This variant is associated with the following publications: (PMID: 26757417, 23108138, 19043619, 28277317, 14973102, 18607349, 9579822, 24323938, 22486713, 18627636, 18779604, 26221963, 11251181, 28222693, 29394989, 26848529, 29681614, 24817641, 31131967, 29884841, 31825140)
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.8702G>A (p.Gly2901Asp)
Germline
Classification
Help
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.
(15)
Help
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.
Benign/Likely benign
15
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.8702G>A (p.Gly2901Asp)
Variation ID: 38180 Accession: VCV000038180.31
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32376739 (GRCh38) [ NCBI UCSC ] 13: 32950876 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Oct 8, 2024 Jan 30, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.8702G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Gly2901Asp missense NC_000013.11:g.32376739G>A NC_000013.10:g.32950876G>A NG_012772.3:g.66260G>A LRG_293:g.66260G>A LRG_293t1:c.8702G>A LRG_293p1:p.Gly2901Asp U43746.1:n.8930G>A - Protein change
- G2901D
- Other names
-
p.G2901D:GGT>GAT
8930G>A
- Canonical SPDI
- NC_000013.11:32376738:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00020 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00007
Exome Aggregation Consortium (ExAC) 0.00012
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
- 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. |
|||
| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18967 | 19126 | |
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. |
|---|---|---|---|---|
| Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Jun 8, 2023 | RCV000031763.22 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 22, 2019 | RCV000130464.18 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 3, 2021 | RCV000590249.15 | |
| Likely benign (1) |
no assertion criteria provided
|
- | RCV002250495.9 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 30, 2024 | RCV001084578.14 | |
| no classifications from unflagged records (1) |
no classifications from unflagged records
|
Oct 16, 2023 | RCV003153312.10 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 2, 2019 | RCV001818200.11 | |
| Likely benign (1) |
no assertion criteria provided
|
Jan 25, 2022 | RCV004532461.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Feb 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210479.12
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 26757417, 23108138, 19043619, 28277317, 14973102, 18607349, 9579822, 24323938, 22486713, 18627636, 18779604, 26221963, 11251181, 28222693, 29394989, 26848529, … (more)
This variant is associated with the following publications: (PMID: 26757417, 23108138, 19043619, 28277317, 14973102, 18607349, 9579822, 24323938, 22486713, 18627636, 18779604, 26221963, 11251181, 28222693, 29394989, 26848529, 29681614, 24817641, 31131967, 29884841, 31825140) (less)
|
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001139225.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Likely benign
(May 02, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000695176.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The c.8702G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Asp. 4/4 in-silico tools predict damaging outcome for … (more)
Variant summary: The c.8702G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Asp. 4/4 in-silico tools predict damaging outcome for this variant. This variant is found in 14/121646 control chromosomes from ExAC at a frequency of 0.0001151. It was predominantly reported in East Asian subpopulation with an allele frequency of 0.0016 which is about 2.15 times higher than the maximum expected allele frequency of a pathogenic variant in this gene suggesting that it is likely to be a polymorphism in East Asians. The variant has been reported in several breast and/or ovarian cancer patients/families, mainly of East Asian origin, without strong evidence for pathogenicity. In one patient with thyroid and breast cancer, a truncating mutation PTEN c. 590delA was also found, possibly suggesting for an alternative disease mechanism. In addition, it was also found in once in each of benign breast cancer patient and healthy control cohorts, possibly suggesting a benign outcome. Functional studies (HDR, cell viability and drug sensitivity assays) shows neutral outcome for this variant. Three out of five clinical labs have also classified this variant as likely benign/benign (other two as uncertain significance). Taken together, this variant has currently been classified as likely benign. (less)
|
|
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Benign
(Sep 07, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001133946.3
First in ClinVar: Jan 04, 2020 Last updated: Jan 03, 2022 |
|
|
|
Likely benign
(Jan 02, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002068243.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Mar 23, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683993.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
|
Benign
(Jan 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000073618.13
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Jun 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846059.1
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)
|
Number of individuals with the variant: 3
|
|
|
Likely benign
(Feb 22, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185329.7
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
|
Likely benign
(Jan 22, 2010)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000054371.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
|
|
Likely benign
(Jan 25, 2022)
|
no assertion criteria provided
Method: clinical testing
|
BRCA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004710855.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: literature only
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Center for Precision Medicine, Meizhou People's Hospital
Accession: SCV002520845.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
|
|
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Uncertain significance
(Jun 12, 2000)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147441.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Geographic origin: Asian
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Chinese
Geographic origin: Malaysia
|
|
|
Likely pathogenic
(Jan 01, 2022)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
Ovarian cancer
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University
Accession: SCV003843612.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
|
|
|
Uncertain significance
(Nov 25, 2015)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000487777.2
First in ClinVar: May 27, 2015 Last updated: Dec 24, 2022 |
|
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| click to load more click to collapse | |||||
| Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more | |||||
Comment:
Comment:
Variant summary: The c.8702G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Asp. 4/4 in-silico tools predict damaging outcome for this variant. This variant is found in 14/121646 control chromosomes from ExAC at a frequency of 0.0001151. It was predominantly reported in East Asian subpopulation with an allele frequency of 0.0016 which is about 2.15 times higher than the maximum expected allele frequency of a pathogenic variant in this gene suggesting that it is likely to be a polymorphism in East Asians. The variant has been reported in several breast and/or ovarian cancer patients/families, mainly of East Asian origin, without strong evidence for pathogenicity. In one patient with thyroid and breast cancer, a truncating mutation PTEN c. 590delA was also found, possibly suggesting for an alternative disease mechanism. In addition, it was also found in once in each of benign breast cancer patient and healthy control cohorts, possibly suggesting a benign outcome. Functional studies (HDR, cell viability and drug sensitivity assays) shows neutral outcome for this variant. Three out of five clinical labs have also classified this variant as likely benign/benign (other two as uncertain significance). Taken together, this variant has currently been classified as likely benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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. |
Comment:
This variant is associated with the following publications: (PMID: 26757417, 23108138, 19043619, 28277317, 14973102, 18607349, 9579822, 24323938, 22486713, 18627636, 18779604, 26221963, 11251181, 28222693, 29394989, 26848529, 29681614, 24817641, 31131967, 29884841, 31825140)
Comment:
Variant summary: The c.8702G>A variant affects a conserved nucleotide, resulting in amino acid change from Gly to Asp. 4/4 in-silico tools predict damaging outcome for this variant. This variant is found in 14/121646 control chromosomes from ExAC at a frequency of 0.0001151. It was predominantly reported in East Asian subpopulation with an allele frequency of 0.0016 which is about 2.15 times higher than the maximum expected allele frequency of a pathogenic variant in this gene suggesting that it is likely to be a polymorphism in East Asians. The variant has been reported in several breast and/or ovarian cancer patients/families, mainly of East Asian origin, without strong evidence for pathogenicity. In one patient with thyroid and breast cancer, a truncating mutation PTEN c. 590delA was also found, possibly suggesting for an alternative disease mechanism. In addition, it was also found in once in each of benign breast cancer patient and healthy control cohorts, possibly suggesting a benign outcome. Functional studies (HDR, cell viability and drug sensitivity assays) shows neutral outcome for this variant. Three out of five clinical labs have also classified this variant as likely benign/benign (other two as uncertain significance). Taken together, this variant has currently been classified as likely benign.
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches. | Guidugli L | American journal of human genetics | 2018 | PMID: 29394989 |
| BRCA1/2 germline missense mutations: a systematic review. | Corso G | European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) | 2018 | PMID: 28277317 |
| Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study. | Lai KN | BMC cancer | 2017 | PMID: 28222693 |
| Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients. | Kim YC | Oncotarget | 2016 | PMID: 26848529 |
| Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing. | Ng PS | Clinical genetics | 2016 | PMID: 26757417 |
| Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population. | Wong ES | PloS one | 2015 | PMID: 26221963 |
| Detection of inherited mutations for hereditary cancer using target enrichment and next generation sequencing. | Guan Y | Familial cancer | 2015 | PMID: 25151137 |
| An integrated in silico approach to analyze the involvement of single amino acid polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 complex. | Doss CG | Cell biochemistry and biophysics | 2014 | PMID: 24817641 |
| A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity. | Guidugli L | Cancer research | 2013 | PMID: 23108138 |
| Detection of BRCA1/2 mutations in breast cancer patients from Thailand and Pakistan. | Ahmad J | Clinical genetics | 2012 | PMID: 22486713 |
| Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. | Karchin R | Cancer informatics | 2008 | PMID: 19043619 |
| Performance of BRCA1/2 mutation prediction models in Asian Americans. | Kurian AW | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18779604 |
| Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. | Thirthagiri E | Breast cancer research : BCR | 2008 | PMID: 18627636 |
| Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. | Kuznetsov SG | Nature medicine | 2008 | PMID: 18607349 |
| BRCA1 and BRCA2 mutations in women from Shanghai China. | Suter NM | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2004 | PMID: 14973102 |
| A missense mutation in the BRCA2 gene in three siblings with ovarian cancer. | Roth S | British journal of cancer | 1998 | PMID: 9579822 |
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Text-mined citations for rs80359129 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 03, 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.