ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.7567_7568del (p.Leu2523fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000059.4(BRCA2):c.7567_7568del (p.Leu2523fs)
Variation ID: 38105 Accession: VCV000038105.21
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 13q13.1 13: 32356554-32356555 (GRCh38) [ NCBI UCSC ] 13: 32930691-32930692 (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 Feb 20, 2024 Sep 8, 2016 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000059.4:c.7567_7568del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Leu2523fs frameshift NM_000059.3:c.7567_7568delCT NC_000013.11:g.32356555CT[2] NC_000013.10:g.32930692CT[2] NG_012772.3:g.46076CT[2] LRG_293:g.46076CT[2] U43746.1:n.7795_7796delCT - Protein change
- L2523fs
- Other names
- 7795delCT
- Canonical SPDI
- NC_000013.11:32356553:TCTCTCT:TCTCT
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
18441 | 18600 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (7) |
reviewed by expert panel
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Sep 8, 2016 | RCV000031687.20 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Apr 20, 2023 | RCV000045250.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 13, 2023 | RCV000563179.11 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 16, 2022 | RCV000507472.12 |
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
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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
(Sep 08, 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: SCV000301178.2
First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
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Pathogenic
(Sep 21, 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: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744522.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018 |
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Pathogenic
(Feb 15, 2017)
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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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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600756.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 03, 2022 |
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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: SCV000327687.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
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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: SCV000267808.1
First in ClinVar: Sep 27, 2014 Last updated: Sep 27, 2014 |
Tissue: Blood
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Pathogenic
(Jun 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001362011.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: BRCA2 c.7567_7568delCT (p.Leu2523GlufsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA2 c.7567_7568delCT (p.Leu2523GlufsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251158 control chromosomes (gnomAD). c.7567_7568delCT has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Gao_2000, van der Hout_2006, Churpek_2015, Sung_2017, Li_2018, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight ClinVar submissions from clinical diagnostic laboratories and an expert panel (ENIGMA)(evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Nov 16, 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: SCV000778884.3
First in ClinVar: Sep 30, 2017 Last updated: Dec 03, 2022 |
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; Truncating … (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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at a significant frequency in large population cohorts (gnomAD); Also known as 7795delCT; This variant is associated with the following publications: (PMID: 11030417, 16683254, 28724667, 30702160, 31825140, 30078507, 30720243, 30787465) (less)
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Pathogenic
(Sep 13, 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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Ambry Genetics
Accession: SCV000665942.5
First in ClinVar: Jan 01, 2018 Last updated: Oct 28, 2023 |
Comment:
The c.7567_7568delCT pathogenic mutation, located in coding exon 14 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7567 to … (more)
The c.7567_7568delCT pathogenic mutation, located in coding exon 14 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 7567 to 7568, causing a translational frameshift with a predicted alternate stop codon (p.L2523Efs*15). This mutation has been seen in multiple families with breast and/or ovarian cancer (Gao Q et al. Hum. Genet., 2000 Aug;107:186-91; Sung PL et al. PLoS ONE, 2017 Sep;12:e0185615; Li A et al. Gynecol. Oncol., 2018 10;151:145-152; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620; Bhaskaran SP et al. Int. J. Cancer, 2019 Aug;145:962-973). Of note, this alteration is also designated as 7795delCT 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)
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Pathogenic
(Apr 20, 2023)
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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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Invitae
Accession: SCV000073263.9
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 38105). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 38105). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 11030417, 16683254). This variant is present in population databases (rs80359664, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Leu2523Glufs*15) 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). (less)
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Pathogenic
(-)
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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
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Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147126.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
Geographic origin: African American
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Pathogenic
(Jan 12, 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: SCV000054294.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
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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: SCV000587900.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733302.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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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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High prevalence of cancer-associated TP53 variants in the gnomAD database: A word of caution concerning the use of variant filtering. | Soussi T | Human mutation | 2019 | PMID: 30720243 |
Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels. | Sung PL | PloS one | 2017 | PMID: 28961279 |
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 |
Inherited predisposition to breast cancer among African American women. | Churpek JE | Breast cancer research and treatment | 2015 | PMID: 25428789 |
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 |
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. | Nanda R | JAMA | 2005 | PMID: 16234499 |
Cancer variation associated with the position of the mutation in the BRCA2 gene. | Lubinski J | Familial cancer | 2004 | PMID: 15131399 |
Inherited BRCA2 mutations in African Americans with breast and/or ovarian cancer: a study of familial and early onset cases. | Kanaan Y | Human genetics | 2003 | PMID: 12942367 |
Breast cancer genetics in African Americans. | Olopade OI | Cancer | 2003 | PMID: 12491487 |
Prevalence of BRCA1 and BRCA2 mutations among clinic-based African American families with breast cancer. | Gao Q | Human genetics | 2000 | PMID: 11030417 |
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Text-mined citations for rs80359664 ...
HelpRecord last updated Mar 23, 2024
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.