Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.5576_5579del (p.Ile1859fs)
Germline
Reviewed by expert panel
Help
Reviewed by expert panel. Learn more about how ClinVar calculates review status.
Pathogenic
for
Breast-ovarian cancer, familial, susceptibility to, 2
Classification is based on the expert panel submission
Apr 2016 by
Evidence-based Network for the Interpretation of Germline M…
Help
The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.5576_5579del (p.Ile1859fs)
Variation ID: 37975 Accession: VCV000037975.99
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 13q13.1 13: 32339929-32339932 (GRCh38) [ NCBI UCSC ] 13: 32914068-32914071 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 1, 2014 Jan 11, 2026 Apr 22, 2016 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.5576_5579del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Ile1859fs frameshift NM_000059.3:c.5574_5577del NM_000059.3:c.5574_5577delAATT NC_000013.11:g.32339931_32339934del NC_000013.10:g.32914068_32914071del NG_012772.3:g.29452_29455del LRG_293:g.29452_29455del LRG_293t1:c.5576_5579del U43746.1:n.5804_5807delTTAA - Protein change
- I1859fs
- Other names
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5803del4
5804_5807delTTAA
5804del4
- Canonical SPDI
- NC_000013.11:32339928:AATTAA:AA
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
21062 | 21226 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (10) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000031556.27 | |
| Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
May 15, 2025 | RCV000044684.36 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 31, 2025 | RCV000131118.23 | |
| Pathogenic (12) |
criteria provided, multiple submitters, no conflicts
|
Dec 29, 2025 | RCV000160296.64 | |
| not provided (1) |
no classification provided
|
- | RCV000509336.11 | |
| Pathogenic (1) |
no assertion criteria provided
|
Mar 10, 2009 | RCV000735566.9 | |
| Pathogenic (3) |
criteria provided, single submitter
|
Mar 25, 2024 | RCV001289538.13 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001353722.10 | |
| Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003162273.8 | |
| Pathogenic (2) |
criteria provided, single submitter
|
Apr 9, 2024 | RCV004732567.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Sep 13, 2024 | RCV004803046.1 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 2, 2024 | RCV005007908.1 | |
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Inherited breast cancer and ovarian cancer
|
Pathogenic (1) |
criteria provided, single submitter
|
Feb 11, 2025 | RCV006436404.1 |
| click to load more conditions click to collapse | ||||
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
Expand all rows
Collapse all rows
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Apr 22, 2016)
C
Contributing to aggregate classification
|
reviewed by expert panel
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282408.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Observation: 1
Collection method: curation
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: curation
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Oct 02, 2015)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327232.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Jul 15, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000605790.4
First in ClinVar: Aug 27, 2017 Last updated: Apr 20, 2024 |
Comment:
show
The p.Ile1859LysfsX3 variant in BRCA2 has been reported in >35 individuals with BRCA2-associated cancers (Saghir 2015 PMID:25777348, Kim 2016 PMID:26848529, Breast Cancer Information Core database (BIC): https://research.nhgri.nih.gov/bic/). It has also been identified in 0.002% (1/41368) African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v3.1). This frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1859 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in HBOC. Additionally, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (Variant ID 37975). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner. ACMG/AMP criteria applied: PS4, PM2_Supporting, PVS1. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Likely pathogenic
(Mar 27, 2023)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome |
Cancer Genomics Group, Japanese Foundation For Cancer Research
Accession: SCV005045660.1
First in ClinVar: Nov 30, 2024 Last updated: Nov 30, 2024 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: no
Observation 1
Collection method: research
Allele origin: germline
Affected status: no
|
|
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Pathogenic
(Apr 09, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
BRCA2-related disorders |
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV005900567.1
First in ClinVar: Mar 29, 2025 Last updated: Mar 29, 2025 |
Comment:
show
This frameshifting variant in exon 11 of 28 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Loss-of-function variation in BRCA2 is an established mechanism of disease (PMID: 20301425). This variant has been previously reported in individuals with breast and ovarian cancer (PMID: 22160602, 23633455, 27914478, 26681312). The c.5576_5579del (p.Ile1859LysfsTer3) variant is present in the heterozygous state in the gnomAD v4 population database at a frequency of 0.002% (30/1605350) and thus is presumed to be rare. Based on the available evidence, c.5576_5579del (p.Ile1859LysfsTer3) is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
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Pathogenic
(Jan 23, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Ambry Genetics
Accession: SCV000186048.9
First in ClinVar: Aug 06, 2014 Last updated: Apr 28, 2025 |
Comment:
show
The c.5576_5579delTTAA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 5576 to 5579, causing a translational frameshift with a predicted alternate stop codon (p.I1859Kfs*3). This mutation has been reported in numerous hereditary breast and ovarian cancer (HBOC) patients and families world-wide (Foster KA et al. Cancer Res. 1996 Aug;56:3622-5; Gonzalez-Angulo AM et al. Clin. Cancer Res. 2011 Mar;17:1082-9; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134:1315-26; Blay P et al. BMC Cancer. 2013 May;13:243; George J et al. Clin. Cancer Res. 2013 Jul;19:3474-84; Song H et al. Hum. Mol. Genet. 2014 Sep;23:4703-9; Kim YC et al. Oncotarget. 2016 Feb;7:9600-12; Susswein LR et al. Genet. Med. 2016 Aug;18:823-32; Maistro S et al. BMC Cancer. 2016 Dec;16:934; Zhao Q et al. J. Gynecol. Oncol. 2017 Jul;28:e39; Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021; Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Momozawa Y et al. Nat Commun, 2018 10;9:4083; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Sunami K et al. Cancer Sci, 2019 Apr;110:1480-1490; Yoshida R et al. Oncotarget, 2019 May;10:3276-3284; Ueda M et al. Obstet Gynecol Int, 2019 May;2019:4365754; El Ansari FZ et al. BMC Cancer, 2020 Aug;20:747; Park CS et al. Asian J Surg, 2020 Oct;43:996-1001; Sirisena N et al. Breast Cancer Res, 2020 05;22:43; Shao D et al. Cancer Sci, 2020 Feb;111:647-657; Bang YJ et al. Cancer Res Treat, 2021 Oct). This mutation has also been identified in patients diagnosed with prostate and biliary tract cancer (Wardell CP et al. J Hepatol, 2018 05;68:959-969; Terashima T et al. Oncotarget, 2019 Oct;10:5949-5957; Momozawa Y et al. J Natl Cancer Inst, 2020 04;112:369-376; Power R et al. Fam Cancer, 2021 04;20:97-101). Of note, this alteration is also designated as c.5574_5577delAATT, 5803delATTA and 5804del4 in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Jan 07, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Revvity Omics, Revvity
Accession: SCV003813750.3
First in ClinVar: Mar 04, 2023 Last updated: Sep 06, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Oct 15, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Not provided |
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001716158.2
First in ClinVar: Jun 15, 2021 Last updated: Jan 11, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Number of individuals with the variant: 2
|
|
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Pathogenic
(Jan 01, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Genologica Medica
Additional submitter:
Servicio Andaluz de Salud, Hospital Universitario Virgen de la Victoria
Accession: SCV000577957.1
First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Test name: BRCAsafe
Family history: yes
Ethnicity/Population group: Causasians
Geographic origin: Spain
Tissue: Blood
Secondary finding: no
Platform type: Sanger sequencing
|
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Pathogenic
(Apr 20, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome |
Department of Pathology and Molecular Medicine, Queen's University
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000588101.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Apr 25, 2016)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome |
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694882.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
show
Variant summary: The c.5576_5579delTTAA variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.5585_5588delTGAA, c.5603_5606delACAG, c.5616_5620delAGTAA). The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.003% which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%). The variant has been cited in numerous affected individuals via the literature and databases, and has been classified by multiple reputable databases and clinical labs as "pathogenic". Taken together, this variant has been classified as as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(Jun 12, 2014)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001449772.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 8
|
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Pathogenic
(Dec 18, 2019)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Not Provided |
GeneDx
Accession: SCV000210767.12
First in ClinVar: Feb 24, 2015 Last updated: Apr 17, 2019 |
Comment:
show
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in a multiple individuals with a personal or family history consistent with pathogenic variants in this gene (Ikeda 2001, Sugano 2008, Wang 2012, Kang 2015, Kim 2016, Eoh 2017, Pritzlaff 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.5574_5577delAATT or 5804del4; This variant is associated with the following publications: (PMID: 22160602, 23683081, 22798144, 28127413, 28541631, 30203341, 11149425, 8705994, 25863477, 23633455, 19016756, 22713736, 24578176, 26848529, 27914478, 28008555, 27633797, 24094589, 28166811, 29422015, 26681312, 28724667, 29348823, 29020732, 29360550, 21643751, 29752822, 29673794, 30287823, 28111427, 30720243, 30742731, 30702160, 30322717, 31143373, 30309222, 31666926, 32300630, 30291343, 29625052, 26689913, 30350268, 31447099, 29176636, 31214711) (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
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Pathogenic
(Jul 12, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Sema4, Sema4
Accession: SCV002536150.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.5576_5579delTTAA (p.I1859Kfs*3) variant has been reported in heterozygosity in numerous individuals with breast and ovarian cancer (PMID: 17262179, 18465347, 20104584, 22713736, 22798144, 30287823, … (more)
The BRCA2 c.5576_5579delTTAA (p.I1859Kfs*3) variant has been reported in heterozygosity in numerous individuals with breast and ovarian cancer (PMID: 17262179, 18465347, 20104584, 22713736, 22798144, 30287823, 33471991). It is also known as 5804del4 in the literature. This variant causes a frameshift at amino acid 1859 that results in premature termination 3 amino acids downstream. At this location, this is predicted to cause nonsense-mediated decay and result in an absent protein (loss of function). Loss of function of the BRCA2 gene is an established disease mechanism in HBOC. This variant was observed in 4/244832 chromosomes from large and broad populations by the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 37975). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
|
Observation: 1
Collection method: curation
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: curation
Allele origin: germline
Affected status: unknown
|
|
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Pathogenic
(May 01, 2021)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Laan Lab, Human Genetics Research Group, University of Tartu
Accession: SCV002538627.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
Observation 1
Collection method: research
Allele origin: unknown
Affected status: unknown
Number of individuals with the variant: 1
Clinical Features:
Non-obstructive azoospermia (present)
Zygosity: Single Heterozygote
Secondary finding: yes
Method: exome sequencing
|
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Pathogenic
(Jan 10, 2017)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000605703.3
First in ClinVar: Mar 27, 2017 Last updated: Dec 11, 2022 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 11
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Pathogenic
(Aug 09, 2023)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296678.7
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
show
The BRCA2 c.5576_5579del (p.Ile1859Lysfs*3) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals and families with breast/ovarian cancer (PMIDs: 35918668 (2022), 34645131 (2022), 31143373 (2019), 30287823 (2018), 23683081 (2013), 23633455 (2013), 22713736 (2012), 22217648 (2012), 22160602 (2012), 20104584 (2010)), and biliary track cancer (PMIDs: 32918181 (2021), 31666926 (2019)). The frequency of this variant in the general population, 0.000016 (4/244832 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
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Pathogenic
(Mar 25, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast |
Baylor Genetics
Accession: SCV004211889.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
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Pathogenic
(Sep 13, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
BRCA2-related cancer predisposition
(Autosomal dominant inheritance)
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846598.2
First in ClinVar: Apr 20, 2024 Last updated: Dec 14, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
show
This variant deletes 4 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5802delTTAA, 5803delATTA, 5804_5808delTTAA, 5804del4 and c.5574_5577delAATT in the literature. This variant is expected to result in unstable variant messenger RNA, which is corroborated by an RNA analysis of allelic imbalance in expressed BRCA2 mRNA transcripts in a heterozygous variant carrier (PMID: 19471317). This variant has been reported in over 30 individuals affected with breast and ovarian cancer (PMID: 8705994, 11149425, 17262179, 20104584, 21233401, 22160602, 22713736, 22798144, 23479189, 23633455, 23683081, 24249303, 24578176, 24728189, 26848529). A Japanese breast cancer case-control study (PMID: 30287823) and a breast cancer case-control meta-analysis (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001464) have reported this variant in 27/7104 cases and 3/23731 unaffected controls and 16/60450 cases and 7/53454 unaffected controls, respectively. This variant also has been reported in a prostate cancer case-control study in 11/7636 prostate cancer cases and 2/12366 unaffected controls (PMID: 31214711). This variant has been identified in 4/244832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Number of individuals with the variant: 10
Zygosity: Single Heterozygote
|
|
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Pathogenic
(Jan 02, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Familial cancer of breast
Medulloblastoma Familial prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 Breast-ovarian cancer, familial, susceptibility to, 2 Glioma susceptibility 3 Pancreatic cancer, susceptibility to, 2
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. |
Fulgent Genetics, Fulgent Genetics
Accession: SCV005633937.1
First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
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Pathogenic
(Jan 29, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000072697.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 25, 2025 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Ile1859Lysfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs770318608, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8705994, 22160602, 22217648, 23633455, 23683081). This variant is also known as 5803delATTA, 5804del4, and 5574_5577delAATT. ClinVar contains an entry for this variant (Variation ID: 37975). For these reasons, this variant has been classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Apr 05, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602738.4
First in ClinVar: Sep 30, 2017 Last updated: Mar 11, 2025 |
Comment:
show
The BRCA2 c.5576_5579delTTAA; p.Ile1859LysfsTer3 variant (rs80359520), also reported as 5802del4, 5803del4 and 5804del4, has been described in the literature in several individuals and families with breast and ovarian cancer (Foster 1996, George 2013, Schneegans 2012). This variant is reported as pathogenic by several sources in the ClinVar database (Variation ID: 37975) and is found in the general population with an overall allele frequency of 0.002% (4/244832 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information this variant is considered pathogenic. References: Foster KA et al. Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. Cancer Res. 1996 56(16):3622-5. PMID: 8705994. George J et al. Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. Clin Cancer Res. 2013 19(13):3474-84. PMID: 23633455. Schneegans SM et al. Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Fam Cancer. 2012 11(2):181-8. PMID: 22160602. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Dec 10, 2024)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Molecular Diagnostics Laboratory, Catalan Institute of Oncology
Additional submitter:
SpadaHC, Centro de Investigación Biomédica en Red Cáncer (CIBERONC)
Accession: SCV006060710.1
First in ClinVar: May 03, 2025 Last updated: May 03, 2025 |
Comment:
show
PVS1, PM5_PTC_Strong c.5576_5579del, located in exon 11 of the BRCA2 gene, consists in the deletion of 4 nucleotides causing a premature protein truncation and nonsense-mediated mRNA decay; p.(Ile1859Lysfs*3)(PVS1, PM5_PTC_Strong). This variant is found in 3/ 230376 in the gnomAD v2.1.1 database, exome non-cancer data set. This variant has been reported in the ClinVar database (36x pathogenic, 1x likely pathogenic) and LOVD (41x pathogenic, 1x uncertain significance, 2x not classified) and classified as a pathogenic variant in BRCA Exchange database (“Variant allele predicted to encode a truncated non-functional protein”). Based on currently available information, the variant c.5576_5579del is classified as a pathogenic variant according to ClinGen-BRCA1 and BRCA2 Guidelines version 1.0.0. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Mar 31, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary cancer-predisposing syndrome |
Color Diagnostics, LLC DBA Color Health
Accession: SCV000292136.5
First in ClinVar: Jul 08, 2016 Last updated: May 03, 2025 |
Comment:
show
This variant deletes 4 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5802delTTAA, 5803delATTA, 5804_5808delTTAA, 5804del4 and c.5574_5577delAATT in the literature. This variant is expected to result in unstable variant messenger RNA, which is corroborated by an RNA analysis of allelic imbalance in expressed BRCA2 mRNA transcripts in a heterozygous variant carrier (PMID: 19471317). This variant has been reported in over 30 individuals affected with breast and ovarian cancer (PMID: 8705994, 11149425, 17262179, 20104584, 21233401, 22160602, 22713736, 22798144, 23479189, 23633455, 23683081, 24249303, 24578176, 24728189, 26848529). A Japanese breast cancer case-control study (PMID: 30287823) and a breast cancer case-control meta-analysis (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001464) have reported this variant in 27/7104 cases and 3/23731 unaffected controls and 16/60450 cases and 7/53454 unaffected controls, respectively. This variant also has been reported in a prostate cancer case-control study in 11/7636 prostate cancer cases and 2/12366 unaffected controls (PMID: 31214711). This variant has been identified in 4/244832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Platform type: NGS
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Pathogenic
(Feb 16, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
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not provided |
Laboratory of Genetics, Children's Clinical University Hospital Latvia
Accession: SCV006108459.1
First in ClinVar: Jul 05, 2025 Last updated: Jul 05, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(May 15, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Hereditary breast ovarian cancer syndrome |
GeneKor MSA
Accession: SCV006311227.1
First in ClinVar: Aug 30, 2025 Last updated: Aug 30, 2025 |
Comment:
show
This variant is a deletion of 4 nucleotides in exon 11 of the BRCA2 mRNA c.(5576_5579delTTAA), causing a frameshift after codon 1859 and the creation of a premature translation stop signal 3 amino acid residues later p.(Ile1859Lysfs*3). This is expected to result in an absent or disrupted protein product. Truncating variants in the BRCA2 gene are known to be pathogenic (PMID:20104584). This variant is present in population databases (rs80359520). This sequence change is also known as 5803delATTA, 5804del4, and 5574_5577delAATT and has been reported in individuals affected with breast and/or ovarian cancer (PMID:23633455, 8705994, 22160602, 22217648). ClinVar contains entries for this variant where is listed as pathogenic (VCV000037975.94). Based on the classification criteria set by the ACMG and AMP (PMID:25741868), this variant has been classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Jun 01, 2020)
N
Not contributing to aggregate classification
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criteria provided, single submitter
|
not provided |
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002563164.23
First in ClinVar: Aug 23, 2022 Last updated: Sep 22, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 3
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Pathogenic
(Dec 29, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
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not provided |
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004027441.4
First in ClinVar: Aug 19, 2023 Last updated: Jan 03, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(Feb 11, 2025)
N
Not contributing to aggregate classification
|
criteria provided, single submitter
|
Inherited breast cancer and ovarian cancer
|
Cambridge Genomics Laboratory, East Genomic Laboratory Hub, NHS Genomic Medicine Service
Accession: SCV007298938.1
First in ClinVar: Jan 11, 2026 Last updated: Jan 11, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(May 29, 2002)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast-ovarian cancer, familial 2 |
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146636.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation:
10
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 5
Observation 2
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 3
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Geographic origin: Western European, Native American
Observation 4
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Observation 5
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European
Observation 6
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Native American
Observation 7
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern Mid East
Observation 8
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 16
Ethnicity/Population group: Western European
Observation 9
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
Observation 10
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
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Pathogenic
(Mar 10, 2009)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast and/or ovarian cancer |
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863704.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Familial cancer of breast |
Center for Precision Medicine, Meizhou People's Hospital
Accession: SCV002520805.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
Observation: 1
Collection method: literature only
Allele origin: germline
Affected status: yes
Observation 1
Collection method: literature only
Allele origin: germline
Affected status: yes
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Pathogenic
(Aug 26, 2022)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
BRCAlab, Lund University
Accession: SCV002588887.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Aug 25, 2015)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Counsyl
Accession: SCV000677685.3
First in ClinVar: Mar 27, 2017 Last updated: Jun 29, 2025 |
Comment:
show
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
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Pathogenic
(May 01, 2012)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast-ovarian cancer, familial 2 |
Sharing Clinical Reports Project (SCRP)
Accession: SCV000054161.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: not provided
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Pathogenic
(Jan 31, 2014)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Hereditary breast ovarian cancer syndrome |
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587774.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: yes
Observation 1
Collection method: research
Allele origin: germline
Affected status: yes
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Pathogenic
(Oct 19, 2019)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Malignant tumor of breast |
Department of Medical Laboratory Science, Faculty of Allied Health Sciences, University of Peradeniya
Accession: SCV001477300.1
First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021
Comment:
frameshift_variant
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Observation 1
Collection method: research
Allele origin: germline
Affected status: yes
Platform type: next-gen sequencing
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Pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
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Malignant tumor of breast |
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591975.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
show
The BRCA2 p.Ile1859Lysfs*3 variant was identified in 72 of 57,640 proband chromosomes (freq: 0.001) from individuals or families with breast or ovarian cancer and in 3 of 47,462 chromosomes (freq: 0.00006) from healthy individuals (Momozawa 2018, Bhaskaran 2019, George 2013, Foster 1996, Haeyoun 2012, Kokichi 2008, Jalkh 2012, Schneegans 2012, Jang 2012, Blay 2013). The variant was identified in dbSNP (rs1255151416) as “NA”, ClinVar (classified as pathogenic by Invitae, Ambry Genetics, Color, GeneDx and 17 other submitters), LOVD 3.0 (observed 35x) and UMD-LSDB (observed 26x). The variant was identified in control databases in 4 of 244,832 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 15,994 chromosomes (freq: 0.0001), European in 2 of 111,564 chromosomes (freq: 0.00002), and East Asian in 1 of 18,154 chromosomes (freq: 0.00006); it was not observed in the Latino, Ashkenazi Jewish, South Asian, Finnish, or Other populations. The p.Ile1859Lysfs*3 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1859 and leads to a premature stop codon 3 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001905806.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001971735.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002034197.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
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Pathogenic
(Jul 01, 2021)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Gastric cancer |
Laboratory for Genotyping Development, RIKEN
Accession: SCV002758332.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: research
Allele origin: germline
Affected status: unknown
|
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Pathogenic
(May 24, 2021)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Breast-ovarian cancer, familial, susceptibility to, 2 |
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)
Accession: SCV005061331.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Observation 1
Collection method: case-control
Allele origin: germline
Affected status: yes
Secondary finding: no
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Pathogenic
(Apr 25, 2024)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
BRCA2-related condition |
PreventionGenetics, part of Exact Sciences
Accession: SCV000805726.2
First in ClinVar: Sep 13, 2018 Last updated: Oct 08, 2024 |
Comment:
show
The BRCA2 c.5576_5579delTTAA variant is predicted to result in a frameshift and premature protein termination (p.Ile1859Lysfs*3). This variant, also described as “c.5803delATTA and 5804del4” in the literature, has been documented in multiple individuals with sporadic/familial breast and/or ovarian cancers (Online Resource 1, Schneegans et al. 2012. PubMed ID: 22160602; George et al. 2013. PubMed ID: 23633455; Maistro et al. 2016. PubMed ID: 27914478; Zhao et al. 2017. PubMed ID: 28541631). This variant is reported in 0.0063% of alleles in individuals of African descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37975/). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
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not provided
(-)
N
Not contributing to aggregate classification
|
no classification provided
|
Hereditary breast ovarian cancer syndrome
Fanconi anemia complementation group D1
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. |
GenomeConnect, ClinGen
Accession: SCV000607032.3
First in ClinVar: Oct 16, 2017 Last updated: Apr 13, 2025 |
Comment:
show
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less)
Observation 1
Collection method: phenotyping only
Allele origin: unknown
Affected status: yes
Clinical Features:
Abnormality of the skull (present) , Hypermetropia (present) , Myopia (present) , Abnormality of urine homeostasis (present) , Abnormality of the bladder (present) , Neoplasm of the skin (present)
Indication for testing: Diagnostic
Test name: Gene Panel Sequencing
Age: 40-49 years
Sex: female
Method: Variant reported as confirmed, but method not specified.
Testing laboratory: Labcorp Genetics (formerly Invitae), Labcorp
Date variant was reported to submitter: 2015-11-23
Testing laboratory interpretation: Pathogenic
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Comment:
Comment:
The p.Ile1859LysfsX3 variant in BRCA2 has been reported in >35 individuals with BRCA2-associated cancers (Saghir 2015 PMID:25777348, Kim 2016 PMID:26848529, Breast Cancer Information Core database (BIC): https://research.nhgri.nih.gov/bic/). It has also been identified in 0.002% (1/41368) African/African American chromosomes by gnomAD (http://gnomad.broadinstitute.org, v3.1). This frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1859 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in HBOC. Additionally, this variant was classified as pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA expert panel (Variant ID 37975). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner. ACMG/AMP criteria applied: PS4, PM2_Supporting, PVS1.
Comment:
This frameshifting variant in exon 11 of 28 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Loss-of-function variation in BRCA2 is an established mechanism of disease (PMID: 20301425). This variant has been previously reported in individuals with breast and ovarian cancer (PMID: 22160602, 23633455, 27914478, 26681312). The c.5576_5579del (p.Ile1859LysfsTer3) variant is present in the heterozygous state in the gnomAD v4 population database at a frequency of 0.002% (30/1605350) and thus is presumed to be rare. Based on the available evidence, c.5576_5579del (p.Ile1859LysfsTer3) is classified as Pathogenic.
Comment:
The c.5576_5579delTTAA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 5576 to 5579, causing a translational frameshift with a predicted alternate stop codon (p.I1859Kfs*3). This mutation has been reported in numerous hereditary breast and ovarian cancer (HBOC) patients and families world-wide (Foster KA et al. Cancer Res. 1996 Aug;56:3622-5; Gonzalez-Angulo AM et al. Clin. Cancer Res. 2011 Mar;17:1082-9; Kim H et al. Breast Cancer Res. Treat. 2012 Aug;134:1315-26; Blay P et al. BMC Cancer. 2013 May;13:243; George J et al. Clin. Cancer Res. 2013 Jul;19:3474-84; Song H et al. Hum. Mol. Genet. 2014 Sep;23:4703-9; Kim YC et al. Oncotarget. 2016 Feb;7:9600-12; Susswein LR et al. Genet. Med. 2016 Aug;18:823-32; Maistro S et al. BMC Cancer. 2016 Dec;16:934; Zhao Q et al. J. Gynecol. Oncol. 2017 Jul;28:e39; Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021; Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Momozawa Y et al. Nat Commun, 2018 10;9:4083; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Liang Y et al. Med Sci Monit, 2018 Apr;24:2465-2475; Ryu JM et al. Breast Cancer Res Treat, 2019 Jan;173:385-395; Sunami K et al. Cancer Sci, 2019 Apr;110:1480-1490; Yoshida R et al. Oncotarget, 2019 May;10:3276-3284; Ueda M et al. Obstet Gynecol Int, 2019 May;2019:4365754; El Ansari FZ et al. BMC Cancer, 2020 Aug;20:747; Park CS et al. Asian J Surg, 2020 Oct;43:996-1001; Sirisena N et al. Breast Cancer Res, 2020 05;22:43; Shao D et al. Cancer Sci, 2020 Feb;111:647-657; Bang YJ et al. Cancer Res Treat, 2021 Oct). This mutation has also been identified in patients diagnosed with prostate and biliary tract cancer (Wardell CP et al. J Hepatol, 2018 05;68:959-969; Terashima T et al. Oncotarget, 2019 Oct;10:5949-5957; Momozawa Y et al. J Natl Cancer Inst, 2020 04;112:369-376; Power R et al. Fam Cancer, 2021 04;20:97-101). Of note, this alteration is also designated as c.5574_5577delAATT, 5803delATTA and 5804del4 in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Comment:
PM5_strong, PVS1
Comment:
Variant summary: The c.5576_5579delTTAA variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (c.5585_5588delTGAA, c.5603_5606delACAG, c.5616_5620delAGTAA). The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.003% which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA2 (0.075%). The variant has been cited in numerous affected individuals via the literature and databases, and has been classified by multiple reputable databases and clinical labs as "pathogenic". Taken together, this variant has been classified as as Pathogenic.
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in a multiple individuals with a personal or family history consistent with pathogenic variants in this gene (Ikeda 2001, Sugano 2008, Wang 2012, Kang 2015, Kim 2016, Eoh 2017, Pritzlaff 2017); Not observed at a significant frequency in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.5574_5577delAATT or 5804del4; This variant is associated with the following publications: (PMID: 22160602, 23683081, 22798144, 28127413, 28541631, 30203341, 11149425, 8705994, 25863477, 23633455, 19016756, 22713736, 24578176, 26848529, 27914478, 28008555, 27633797, 24094589, 28166811, 29422015, 26681312, 28724667, 29348823, 29020732, 29360550, 21643751, 29752822, 29673794, 30287823, 28111427, 30720243, 30742731, 30702160, 30322717, 31143373, 30309222, 31666926, 32300630, 30291343, 29625052, 26689913, 30350268, 31447099, 29176636, 31214711)
Comment:
The BRCA2 c.5576_5579del (p.Ile1859Lysfs*3) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals and families with breast/ovarian cancer (PMIDs: 35918668 (2022), 34645131 (2022), 31143373 (2019), 30287823 (2018), 23683081 (2013), 23633455 (2013), 22713736 (2012), 22217648 (2012), 22160602 (2012), 20104584 (2010)), and biliary track cancer (PMIDs: 32918181 (2021), 31666926 (2019)). The frequency of this variant in the general population, 0.000016 (4/244832 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Comment:
This variant deletes 4 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5802delTTAA, 5803delATTA, 5804_5808delTTAA, 5804del4 and c.5574_5577delAATT in the literature. This variant is expected to result in unstable variant messenger RNA, which is corroborated by an RNA analysis of allelic imbalance in expressed BRCA2 mRNA transcripts in a heterozygous variant carrier (PMID: 19471317). This variant has been reported in over 30 individuals affected with breast and ovarian cancer (PMID: 8705994, 11149425, 17262179, 20104584, 21233401, 22160602, 22713736, 22798144, 23479189, 23633455, 23683081, 24249303, 24578176, 24728189, 26848529). A Japanese breast cancer case-control study (PMID: 30287823) and a breast cancer case-control meta-analysis (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001464) have reported this variant in 27/7104 cases and 3/23731 unaffected controls and 16/60450 cases and 7/53454 unaffected controls, respectively. This variant also has been reported in a prostate cancer case-control study in 11/7636 prostate cancer cases and 2/12366 unaffected controls (PMID: 31214711). This variant has been identified in 4/244832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Ile1859Lysfs*3) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs770318608, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8705994, 22160602, 22217648, 23633455, 23683081). This variant is also known as 5803delATTA, 5804del4, and 5574_5577delAATT. ClinVar contains an entry for this variant (Variation ID: 37975). For these reasons, this variant has been classified as Pathogenic.
Comment:
The BRCA2 c.5576_5579delTTAA; p.Ile1859LysfsTer3 variant (rs80359520), also reported as 5802del4, 5803del4 and 5804del4, has been described in the literature in several individuals and families with breast and ovarian cancer (Foster 1996, George 2013, Schneegans 2012). This variant is reported as pathogenic by several sources in the ClinVar database (Variation ID: 37975) and is found in the general population with an overall allele frequency of 0.002% (4/244832 alleles) in the Genome Aggregation Database. This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information this variant is considered pathogenic. References: Foster KA et al. Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. Cancer Res. 1996 56(16):3622-5. PMID: 8705994. George J et al. Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. Clin Cancer Res. 2013 19(13):3474-84. PMID: 23633455. Schneegans SM et al. Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Fam Cancer. 2012 11(2):181-8. PMID: 22160602.
Comment:
PVS1, PM5_PTC_Strong c.5576_5579del, located in exon 11 of the BRCA2 gene, consists in the deletion of 4 nucleotides causing a premature protein truncation and nonsense-mediated mRNA decay; p.(Ile1859Lysfs*3)(PVS1, PM5_PTC_Strong). This variant is found in 3/ 230376 in the gnomAD v2.1.1 database, exome non-cancer data set. This variant has been reported in the ClinVar database (36x pathogenic, 1x likely pathogenic) and LOVD (41x pathogenic, 1x uncertain significance, 2x not classified) and classified as a pathogenic variant in BRCA Exchange database (“Variant allele predicted to encode a truncated non-functional protein”). Based on currently available information, the variant c.5576_5579del is classified as a pathogenic variant according to ClinGen-BRCA1 and BRCA2 Guidelines version 1.0.0.
Comment:
This variant deletes 4 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 5802delTTAA, 5803delATTA, 5804_5808delTTAA, 5804del4 and c.5574_5577delAATT in the literature. This variant is expected to result in unstable variant messenger RNA, which is corroborated by an RNA analysis of allelic imbalance in expressed BRCA2 mRNA transcripts in a heterozygous variant carrier (PMID: 19471317). This variant has been reported in over 30 individuals affected with breast and ovarian cancer (PMID: 8705994, 11149425, 17262179, 20104584, 21233401, 22160602, 22713736, 22798144, 23479189, 23633455, 23683081, 24249303, 24578176, 24728189, 26848529). A Japanese breast cancer case-control study (PMID: 30287823) and a breast cancer case-control meta-analysis (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001464) have reported this variant in 27/7104 cases and 3/23731 unaffected controls and 16/60450 cases and 7/53454 unaffected controls, respectively. This variant also has been reported in a prostate cancer case-control study in 11/7636 prostate cancer cases and 2/12366 unaffected controls (PMID: 31214711). This variant has been identified in 4/244832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This variant is a deletion of 4 nucleotides in exon 11 of the BRCA2 mRNA c.(5576_5579delTTAA), causing a frameshift after codon 1859 and the creation of a premature translation stop signal 3 amino acid residues later p.(Ile1859Lysfs*3). This is expected to result in an absent or disrupted protein product. Truncating variants in the BRCA2 gene are known to be pathogenic (PMID:20104584). This variant is present in population databases (rs80359520). This sequence change is also known as 5803delATTA, 5804del4, and 5574_5577delAATT and has been reported in individuals affected with breast and/or ovarian cancer (PMID:23633455, 8705994, 22160602, 22217648). ClinVar contains entries for this variant where is listed as pathogenic (VCV000037975.94). Based on the classification criteria set by the ACMG and AMP (PMID:25741868), this variant has been classified as pathogenic.
Comment:
Classification criteria: PVS1, PM5_strong
Comment:
PVS1,PS4_Very Strong,PM5_Strong
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
Comment:
The BRCA2 p.Ile1859Lysfs*3 variant was identified in 72 of 57,640 proband chromosomes (freq: 0.001) from individuals or families with breast or ovarian cancer and in 3 of 47,462 chromosomes (freq: 0.00006) from healthy individuals (Momozawa 2018, Bhaskaran 2019, George 2013, Foster 1996, Haeyoun 2012, Kokichi 2008, Jalkh 2012, Schneegans 2012, Jang 2012, Blay 2013). The variant was identified in dbSNP (rs1255151416) as “NA”, ClinVar (classified as pathogenic by Invitae, Ambry Genetics, Color, GeneDx and 17 other submitters), LOVD 3.0 (observed 35x) and UMD-LSDB (observed 26x). The variant was identified in control databases in 4 of 244,832 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 15,994 chromosomes (freq: 0.0001), European in 2 of 111,564 chromosomes (freq: 0.00002), and East Asian in 1 of 18,154 chromosomes (freq: 0.00006); it was not observed in the Latino, Ashkenazi Jewish, South Asian, Finnish, or Other populations. The p.Ile1859Lysfs*3 variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1859 and leads to a premature stop codon 3 codons downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.
Comment:
The BRCA2 c.5576_5579delTTAA variant is predicted to result in a frameshift and premature protein termination (p.Ile1859Lysfs*3). This variant, also described as “c.5803delATTA and 5804del4” in the literature, has been documented in multiple individuals with sporadic/familial breast and/or ovarian cancers (Online Resource 1, Schneegans et al. 2012. PubMed ID: 22160602; George et al. 2013. PubMed ID: 23633455; Maistro et al. 2016. PubMed ID: 27914478; Zhao et al. 2017. PubMed ID: 28541631). This variant is reported in 0.0063% of alleles in individuals of African descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/37975/). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain). | Pitiot AS | Clinical genetics | 2024 | PMID: 38922859 |
| High Frequency of BRCA2 c.5576_5579del Carriers in Kakogawa, Japan. | Nakamura H | Cancer diagnosis & prognosis | 2024 | PMID: 38707742 |
| Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
| Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients. | Zhang Y | BMC cancer | 2022 | PMID: 35918668 |
| Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management. | Kasak L | Human reproduction (Oxford, England) | 2022 | PMID: 35535697 |
| Clinicopathological Characterization of Double Heterozygosity for BRCA1 and BRCA2 Variants in Korean Breast Cancer Patients. | Bang YJ | Cancer research and treatment | 2022 | PMID: 34645131 |
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants. | Power R | Familial cancer | 2021 | PMID: 32918181 |
| Genetic characterization of pancreatic cancer patients and prediction of carrier status of germline pathogenic variants in cancer-predisposing genes. | Mizukami K | EBioMedicine | 2020 | PMID: 32980694 |
| Screening of BRCA1/2 genes mutations and copy number variations in patients with high risk for hereditary breast and ovarian cancer syndrome (HBOC). | El Ansari FZ | BMC cancer | 2020 | PMID: 32778078 |
| Functional evaluation of five BRCA2 unclassified variants identified in a Sri Lankan cohort with inherited cancer syndromes using a mouse embryonic stem cell-based assay. | Sirisena N | Breast cancer research : BCR | 2020 | PMID: 32393398 |
| Comparison of clinical features and oncologic outcomes between familial non-hereditary and hereditary breast cancer in Korean female patients. | Park CS | Asian journal of surgery | 2020 | PMID: 31924417 |
| Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high-risk Chinese individuals. | Shao D | Cancer science | 2020 | PMID: 31742824 |
| Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls. | Momozawa Y | Journal of the National Cancer Institute | 2020 | PMID: 31214711 |
| Germline mutations in cancer-predisposition genes in patients with biliary tract cancer. | Terashima T | Oncotarget | 2019 | PMID: 31666926 |
| Challenges in Managing Patients with Hereditary Cancer at Gynecological Services. | Ueda M | Obstetrics and gynecology international | 2019 | PMID: 31263500 |
| Analysis of clinical characteristics of breast cancer patients with the Japanese founder mutation BRCA1 L63X. | Yoshida R | Oncotarget | 2019 | PMID: 31143373 |
| Feasibility and utility of a panel testing for 114 cancer-associated genes in a clinical setting: A hospital-based study. | Sunami K | Cancer science | 2019 | PMID: 30742731 |
| Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea. | Ryu JM | Breast cancer research and treatment | 2019 | PMID: 30350268 |
| Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
| Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
| Prevalence and Spectrum of BRCA1/2 Germline Mutations in Women with Breast Cancer in China Based on Next-Generation Sequencing. | Liang Y | Medical science monitor : international medical journal of experimental and clinical research | 2018 | PMID: 29681614 |
| Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations. | Wardell CP | Journal of hepatology | 2018 | PMID: 29360550 |
| Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
| Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls. | Park JS | Cancer research and treatment | 2017 | PMID: 28111427 |
| Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil. | Maistro S | BMC cancer | 2016 | PMID: 27914478 |
| Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients. | Kim YC | Oncotarget | 2016 | PMID: 26848529 |
| BRCA1 and BRCA2 mutations in ethnic Lebanese Arab women with high hereditary risk breast cancer. | El Saghir NS | The oncologist | 2015 | PMID: 25777348 |
| Prevalence and differentiation of hereditary breast and ovarian cancers in Japan. | Nakamura S | Breast cancer (Tokyo, Japan) | 2015 | PMID: 24249303 |
| The contribution of deleterious germline mutations in BRCA1, BRCA2 and the mismatch repair genes to ovarian cancer in the population. | Song H | Human molecular genetics | 2014 | PMID: 24728189 |
| Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history. | Kang PC | Breast cancer research and treatment | 2014 | PMID: 24578176 |
| Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain). | Blay P | BMC cancer | 2013 | PMID: 23683081 |
| Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations. | George J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2013 | PMID: 23633455 |
| Novel and recurrent BRCA1/BRCA2 mutations in early onset and familial breast and ovarian cancer detected in the Program of Genetic Counseling in Cancer of Valencian Community (eastern Spain). Relationship of family phenotypes with mutation prevalence. | de Juan Jiménez I | Familial cancer | 2013 | PMID: 23479189 |
| Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer. | Kim H | Breast cancer research and treatment | 2012 | PMID: 22798144 |
| Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
| Prevalance of BRCA1 and BRCA2 mutations in familial breast cancer patients in Lebanon. | Jalkh N | Hereditary cancer in clinical practice | 2012 | PMID: 22713736 |
| Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing. | Jang JH | Journal of human genetics | 2012 | PMID: 22217648 |
| Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. | Schneegans SM | Familial cancer | 2012 | PMID: 22160602 |
| The Korean Hereditary Breast Cancer (KOHBRA) study: protocols and interim report. | Han SA | Clinical oncology (Royal College of Radiologists (Great Britain)) | 2011 | PMID: 21497495 |
| Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. | Gonzalez-Angulo AM | Clinical cancer research : an official journal of the American Association for Cancer Research | 2011 | PMID: 21233401 |
| EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients. | Caux-Moncoutier V | Human mutation | 2011 | PMID: 21120943 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Impact of BRCA1 and BRCA2 variants on splicing: clues from an allelic imbalance study. | Caux-Moncoutier V | European journal of human genetics : EJHG | 2009 | PMID: 19471317 |
| BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer. | Thomassen M | Acta oncologica (Stockholm, Sweden) | 2008 | PMID: 18465347 |
| Differences in the frequency and distribution of BRCA1 and BRCA2 mutations in breast/ovarian cancer cases from the Basque country with respect to the Spanish population: implications for genetic counselling. | Beristain E | Breast cancer research and treatment | 2007 | PMID: 17262179 |
| Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. | Ikeda N | International journal of cancer | 2001 | PMID: 11149425 |
| Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. | Foster KA | Cancer research | 1996 | PMID: 8705994 |
| https://spadahc.ciberisciii.es/variant/GRCH37/13%2032914066%20AATT/- | - | - | - | - |
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Record last updated Jan 11, 2026
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.