ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.8297del (p.Thr2766fs)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.8297del (p.Thr2766fs)
Variation ID: 38149 Accession: VCV000038149.42
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 13q13.1 13: 32363499 (GRCh38) [ NCBI UCSC ] 13: 32937636 (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 12, 2013 Jan 13, 2025 Apr 22, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.8297del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Thr2766fs frameshift NM_000059.3:c.8297delC NC_000013.11:g.32363499del NC_000013.10:g.32937636del NG_012772.3:g.53020del LRG_293:g.53020del U43746.1:n.8525delC - Protein change
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- Other names
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8525delC
- Canonical SPDI
- NC_000013.11:32363498:C:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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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The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- 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 | ||
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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 |
19280 | 19437 |
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. |
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Pathogenic (8) |
reviewed by expert panel
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Apr 22, 2016 | RCV000031732.22 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 10, 2024 | RCV000034463.27 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Sep 12, 2023 | RCV000045466.25 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Oct 8, 2024 | RCV000163359.22 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2015 | RCV000210122.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 15, 2022 | RCV002477039.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 12, 2024 | RCV003473217.2 | |
Pathogenic (1) |
no assertion criteria provided
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Nov 16, 2023 | RCV004532459.2 |
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. |
More information
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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Pathogenic
(Apr 22, 2016)
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reviewed by expert panel
Method: curation
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282457.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Apr 21, 2016)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267818.1
First in ClinVar: Sep 27, 2014 Last updated: Sep 27, 2014 |
Tissue: Blood
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Pathogenic
(Jan 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000210793.16
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
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 … (more)
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 individuals with a personal and/or family history of BRCA2-related cancers (Tavtigian 1996, Evans 2003, Edwards 2010, Willems-Jones 2012, McVeigh 2014, Pritzlaff 2017); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 8525delC; This variant is associated with the following publications: (PMID: 12474142, 20736950, 12960223, 30609409, 12181777, 26046366, 25682074, 26681312, 23035815, 23884708, 8589730, 23028338, 28008555, 25085752, 22703879, 26845104, 31090900, 26295337, 25685387, 23569316, 10682686, 31569370, 32853339, 30787465, 33087929) (less)
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Pathogenic
(Mar 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004565285.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
The BRCA2 c.8297del; p.Thr2766AsnfsTer11 variant (rs80359705), also known as 8525delC, is reported in individuals with hereditary breast and ovarian cancer syndrome (Edwards 2010, Lilyquist 2017, … (more)
The BRCA2 c.8297del; p.Thr2766AsnfsTer11 variant (rs80359705), also known as 8525delC, is reported in individuals with hereditary breast and ovarian cancer syndrome (Edwards 2010, Lilyquist 2017, Tavtigian 1996). This variant is also reported in ClinVar (Variation ID: 38149). It is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, 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 to be pathogenic. References: Edwards SM et al. Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. Br J Cancer. 2010 Sep 7;103(6):918-24. PMID: 20736950. Lilyquist J et al. Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls. Gynecol Oncol. 2017 Nov;147(2):375-380. PMID: 28888541. Tavtigian SV et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 1996 Mar;12(3):333-7. PMID: 8589730. (less)
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Pathogenic
(Jul 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695139.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The BRCA2 c.8297delC (p.Thr2766Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense … (more)
Variant summary: The BRCA2 c.8297delC (p.Thr2766Asnfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not found in controls (ExAC, 1000 Gs or ESP). Multiple publications cite the variant in affected individuals, along with multiple reputable databases/clinical laboratories citing the variant as "pathogenic." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Pathogenic. (less)
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Pathogenic
(Mar 15, 2022)
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criteria provided, single submitter
Method: clinical testing
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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
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002780679.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Sep 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000296689.6
First in ClinVar: Jun 24, 2016 Last updated: Jan 06, 2024 |
Comment:
The BRCA2 c.8297del (p.Thr2766Asnfs*11) variant has been reported in the published literature in individuals and families affected with breast and/or ovarian cancer (PMIDs: 8589730 (1996), … (more)
The BRCA2 c.8297del (p.Thr2766Asnfs*11) variant has been reported in the published literature in individuals and families affected with breast and/or ovarian cancer (PMIDs: 8589730 (1996), 10682686 (2000), 26681312 (2015)) and prostate cancer (PMIDs: 20736950 (2010), 23569316 (2013)). The frequency of this variant in the general population, 0.0000066 (1/152178 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Feb 12, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211850.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Oct 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000213895.8
First in ClinVar: Mar 24, 2015 Last updated: Jan 13, 2025 |
Comment:
The c.8297delC (p.T2766Nfs*11) alteration, located in exon 18 (coding exon 17) of the BRCA2 gene, consists of a deletion of one nucleotide at position 8297, … (more)
The c.8297delC (p.T2766Nfs*11) alteration, located in exon 18 (coding exon 17) of the BRCA2 gene, consists of a deletion of one nucleotide at position 8297, causing a translational frameshift with a predicted alternate stop codon after 11 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This mutation was reported in one family with multiple cases of female and male breast cancer and ovarian cancer (Tavtigian, 1996). This alteration has also been reported in multiple men diagnosed with prostate cancer before the age of 55 (Edwards, 2010; Willems-Jones, 2012; Castro, 2013). Of note, this alteration is also designated as 8525delC in published literature. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(Nov 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266047.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 50-59 years
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Pathogenic
(Apr 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586981.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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Pathogenic
(Apr 16, 2018)
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criteria provided, single submitter
Method: research
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
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HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Study: CSER-HudsonAlpha
Accession: SCV000778589.1 First in ClinVar: Sep 28, 2017 Last updated: Sep 28, 2017 |
Number of individuals with the variant: 1
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Pathogenic
(May 23, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000803159.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
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Pathogenic
(Feb 22, 2018)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
(Autosomal dominant inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966960.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Thr2766AsnfsX11 (NM_000059.3 c.8297delC) variant in BRCA2 (also referred t o as c.8285delC in the literature) has been previously reported in many individu als and … (more)
The p.Thr2766AsnfsX11 (NM_000059.3 c.8297delC) variant in BRCA2 (also referred t o as c.8285delC in the literature) has been previously reported in many individu als and families with breast, ovarian or prostate cancer (Tavtigian 1996, Castro 2013, McVeigh 2014, Wong-Brown 2015), and was absent from large population stud ies. In addition, this variant was classified as Pathogenic by the ClinGen-appr oved ENIGMA expert panel (ClinVar SCV000282457.1). This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 2766 and leads to a premature termination codon 11 amino acids downstre am. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of BRCA2 function is an established disease mechanism in here ditary breast and ovarian cancer syndrome (HBOC). In summary, this variant meets our criteria to be classified as pathogenic for HBOC in an autosomal dominant m anner based on its occurrence in affected individuals and its predicted impact t o the protein. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Moderate, PP5 (Richards 2015). (less)
Number of individuals with the variant: 2
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Pathogenic
(Sep 01, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002531929.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BRCA2 c.8297delC (p.T2766NfsX11) variant has been reported in heterozygosity in numerous individuals with female and male breast cancer, as well as individuals with ovarian … (more)
The BRCA2 c.8297delC (p.T2766NfsX11) variant has been reported in heterozygosity in numerous individuals with female and male breast cancer, as well as individuals with ovarian and prostate cancer (PMID: 29446198, 8589730, 12474142, 23035815, 31090900, etc.). It is also reported as 8525delC in the literature. This variant is a well-established pathogenic variant associated with hereditary breast and ovarian cancer syndrome (PMID: 29446198). This variant causes a frameshift at amino acid 2766 that results in premature termination 11 amino acids downstream. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants in BRCA2 are known to be pathogenic (PMID: 29446198). This variant is not reported in the population database Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 38149). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Oct 02, 2015)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
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Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000327853.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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Pathogenic
(Apr 13, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV003810423.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
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Pathogenic
(Nov 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000683953.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 1 nucleotide in exon 18 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 18 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in 9 individuals affected with breast or ovarian cancer (PMID: 10682686, 12960223, 23146383, 25682074, 26681312, 26845104, 33471991), 3 individuals affected with prostate cancer (PMID: 20736950, 23569316), and 1 unaffected individual (PMID: 33471991). This variant has been identified in 70 families among the CIMBA participants (PMID: 29446198). This variant has not been identified 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)
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Pathogenic
(Jan 10, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000073479.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr2766Asnfs*11) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Thr2766Asnfs*11) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast, ovarian and/or prostate cancer (PMID: 8589730, 10682686, 12960223, 20736950, 23028338, 25085752, 26681312). This variant is also known as 8525delC. ClinVar contains an entry for this variant (Variation ID: 38149). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004845630.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 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)
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Comment:
This variant deletes 1 nucleotide in exon 18 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 18 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in 9 individuals affected with breast or ovarian cancer (PMID: 10682686, 12960223, 23146383, 25682074, 26681312, 26845104, 33471991), 3 individuals affected with prostate cancer (PMID: 20736950, 23569316), and 1 unaffected individual (PMID: 33471991). This variant has been identified in 70 families among the CIMBA participants (PMID: 29446198). This variant has not been identified 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)
Number of individuals with the variant: 4
Zygosity: Single Heterozygote
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Pathogenic
(Mar 01, 1996)
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no assertion criteria provided
Method: literature only
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BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030129.2
First in ClinVar: Apr 04, 2013 Last updated: Apr 26, 2015 |
Comment on evidence:
In 10 of 18 breast cancer families (BROVCA2; 612555) selected on the basis of linkage analysis and/or the presence of 1 or more cases of … (more)
In 10 of 18 breast cancer families (BROVCA2; 612555) selected on the basis of linkage analysis and/or the presence of 1 or more cases of male breast cancer, Tavtigian et al. (1996) identified microdeletions in the BRCA2 gene. One of the microdeletions involved nucleotide C8525 in codon 2766. This deletion caused a frameshift, generating a termination signal at codon 2776. (less)
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Pathogenic
(Jan 31, 2014)
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no assertion criteria provided
Method: research
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587944.1 First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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pathogenic
(Jul 13, 2012)
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no assertion criteria provided
Method: research
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Breast-ovarian cancer, familial
Affected status: no
Allele origin:
germline
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Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043230.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Pathogenic.
Number of individuals with the variant: 1
Age: 50-59 years
Sex: male
Ethnicity/Population group: Irish
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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Pathogenic
(May 29, 2002)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline,
unknown
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147316.2
First in ClinVar: Apr 01, 2014 Last updated: Sep 27, 2014 |
Observation 1:
Number of individuals with the variant: 13
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Central/Eastern European
Observation 3:
Number of individuals with the variant: 1
Geographic origin: English
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Ireland
Observation 5:
Number of individuals with the variant: 1
Geographic origin: Native American
Observation 6:
Number of individuals with the variant: 2
Geographic origin: Western European
Observation 7:
Number of individuals with the variant: 1
Geographic origin: Western European, Central Eastern European
Observation 8:
Number of individuals with the variant: 18
Ethnicity/Population group: Western European
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Caucasian
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Ireland
Observation 11:
Number of individuals with the variant: 1
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Pathogenic
(May 01, 2012)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
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Sharing Clinical Reports Project (SCRP)
Accession: SCV000054339.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
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Pathogenic
(Nov 16, 2023)
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no assertion criteria provided
Method: clinical testing
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BRCA2-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004729565.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The BRCA2 c.8297delC variant is predicted to result in a frameshift and premature protein termination (p.Thr2766Asnfs*11). This variant (also known as 8525delC) has been reported … (more)
The BRCA2 c.8297delC variant is predicted to result in a frameshift and premature protein termination (p.Thr2766Asnfs*11). This variant (also known as 8525delC) has been reported in individuals with breast, ovarian, or prostate cancer (Table 1, Tavtigian et al. 1996. PubMed ID: 8589730; Table 1, Edwards et al. 2003. PubMed ID: 12474142; Table 1, Edwards et al. 2010. PubMed ID: 20736950, Table 2, Wong-Brown et al. 2015. PubMed ID: 25682074; Table S7, Lilyquist et al. 2017. PubMed ID: 28888541). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been reviewed by an expert panel and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/38149/). Frameshift variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Landscape of germline pathogenic variants in patients with dual primary breast and lung cancer. | Lee NY | Human genomics | 2023 | PMID: 37461096 |
Penetrance of pathogenic genetic variants associated with premature ovarian insufficiency. | Shekari S | Nature medicine | 2023 | PMID: 37349538 |
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 |
Prostate Cancer Risk by BRCA2 Genomic Regions. | Nyberg T | European urology | 2020 | PMID: 32532514 |
A Functional Analysis of the Unclassified Pro2767Ser BRCA2 Variant Reveals Its Potential Pathogenicity that Acts by Hampering DNA Binding and Homology-Mediated DNA Repair. | Esposito MV | Cancers | 2019 | PMID: 31569370 |
Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers. | Nones K | Annals of oncology : official journal of the European Society for Medical Oncology | 2019 | PMID: 31090900 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
Improving performance of multigene panels for genomic analysis of cancer predisposition. | Shirts BH | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26845104 |
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. | Susswein LR | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26681312 |
Individualized iterative phenotyping for genome-wide analysis of loss-of-function mutations. | Johnston JJ | American journal of human genetics | 2015 | PMID: 26046366 |
Diagnostic Screening Workflow for Mutations in the BRCA1 and BRCA2 Genes. | Lai S | Sultan Qaboos University medical journal | 2015 | PMID: 25685387 |
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. | Wong-Brown MW | Breast cancer research and treatment | 2015 | PMID: 25682074 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
Familial breast cancer genetic testing in the West of Ireland. | McVeigh TP | Irish journal of medical science | 2014 | PMID: 23884708 |
Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. | Castro E | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2013 | PMID: 23569316 |
Genotypic and phenotypic analysis of familial male breast cancer shows under representation of the HER2 and basal subtypes in BRCA-associated carcinomas. | Deb S | BMC cancer | 2012 | PMID: 23146383 |
High grade prostatic intraepithelial neoplasia does not display loss of heterozygosity at the mutation locus in BRCA2 mutation carriers with aggressive prostate cancer. | Willems-Jones A | BJU international | 2012 | PMID: 23035815 |
Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. | Thompson ER | PLoS genetics | 2012 | PMID: 23028338 |
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. | Johnston JJ | American journal of human genetics | 2012 | PMID: 22703879 |
Prostate cancer in BRCA2 germline mutation carriers is associated with poorer prognosis. | Edwards SM | British journal of cancer | 2010 | PMID: 20736950 |
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 |
Sensitivity of BRCA1/2 mutation testing in 466 breast/ovarian cancer families. | Evans DG | Journal of medical genetics | 2003 | PMID: 12960223 |
Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene. | Edwards SM | American journal of human genetics | 2003 | PMID: 12474142 |
Contribution of BRCA1 and BRCA2 mutations to breast and ovarian cancer in Pakistan. | Liede A | American journal of human genetics | 2002 | PMID: 12181777 |
Evidence of a founder BRCA1 mutation in Scotland. | Liede A | British journal of cancer | 2000 | PMID: 10682686 |
Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations. | Spain BH | Proceedings of the National Academy of Sciences of the United States of America | 1999 | PMID: 10570174 |
The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. | Tavtigian SV | Nature genetics | 1996 | PMID: 8589730 |
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Text-mined citations for rs80359705 ...
HelpRecord last updated Jan 13, 2025
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.