ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.8149G>T (p.Ala2717Ser)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.8149G>T (p.Ala2717Ser)
Variation ID: 41564 Accession: VCV000041564.89
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32363351 (GRCh38) [ NCBI UCSC ] 13: 32937488 (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 12, 2013 Oct 8, 2024 Jun 11, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.8149G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Ala2717Ser missense NC_000013.11:g.32363351G>T NC_000013.10:g.32937488G>T NG_012772.3:g.52872G>T LRG_293:g.52872G>T LRG_293t1:c.8149G>T LRG_293p1:p.Ala2717Ser U43746.1:n.8377G>T - Protein change
- A2717S
- Other names
- p.A2717S:GCC>TCC
- NP_000050.3:p.Ala2717Ser
- NM_000059.4(BRCA2):c.8149G>T
- 8377G>T
- Canonical SPDI
- NC_000013.11:32363350:G:T
-
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.
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0.00060 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00105
The Genome Aggregation Database (gnomAD) 0.00127
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00146
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00062
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 |
18951 | 19110 |
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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Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000045431.29 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000034461.46 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Sep 8, 2020 | RCV000129099.17 | |
Conflicting interpretations of pathogenicity (8) |
criteria provided, conflicting classifications
|
Aug 15, 2023 | RCV000120361.41 | |
Benign/Likely benign (13) |
reviewed by expert panel
|
Feb 5, 2024 | RCV000083145.32 | |
Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000280295.13 | |
Benign (2) |
criteria provided, single submitter
|
Apr 17, 2023 | RCV000735609.13 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001353905.9 | |
Likely benign (1) |
no assertion criteria provided
|
May 1, 2024 | RCV004528156.2 | |
Benign (1) |
reviewed by expert panel
|
Jun 11, 2024 | RCV004566799.1 |
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. |
|
---|---|---|---|---|---|
Benign
(Jun 11, 2024)
|
reviewed by expert panel
Method: curation
|
BRCA2-related cancer predisposition
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV004101441.3 First in ClinVar: Nov 11, 2023 Last updated: Jun 17, 2024 |
Comment:
The c.8149G>T variant in BRCA2 is a missense variant predicted to cause substitution of Alanine by Serine at amino acid 2717 (p.Ala2717Ser). The highest non-cancer, … (more)
The c.8149G>T variant in BRCA2 is a missense variant predicted to cause substitution of Alanine by Serine at amino acid 2717 (p.Ala2717Ser). The highest non-cancer, non-founder population filter allele frequency in gnomAD v2.1 (exomes only, non-cancer subset, read depth >=20) or gnomAD v3.1 (non-cancer subset, read depth >=20) is 0.001751 in the Latino/Admixed American population, which is above the ENIGMA BRCA1/2 VCEP threshold (>0.001) for BA1 (BA1 met). This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of -0.0816, which is below the recommended threshold of 0.18 for predicting no impact on BRCA2 via protein change. SpliceAI predictor score of 0.03 suggests that the variant has no impact on splicing (score threshold <0.10) (BP4 met). Reported by 3 calibrated studies to exhibit protein function similar to benign control variants (PMIDs: 29988080, 33609447, 32444794) (BS3 met). This variant has been observed in 2 individuals with features considered inconsistent with an FA-associated phenotype, and (Likely) Pathogenic variant seen in trans or variant is homozygous (total score 4 points) (BS2 met; Invitae internal contributor). Multifactorial likelihood ratio analysis using clinically calibrated data produced a combined LR for this variant of 2.288E-117 (based on Cosegregation LR=4.52E-08; Pathology LR=5.249E-08; Family History LR=1.995E-19; Case-Control LR=4.83E-84), below the threshold for Very strong benign evidence (LR <0.00285) (BP5_Very strong met; PMID: Internal lab contributors). In summary, this variant meets the criteria to be classified as a Benign variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (BA1, BP4, BS3, BS2, BP5_Very strong). (less)
|
|
Benign
(Nov 19, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000183810.7
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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
(Sep 22, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002070556.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
Benign
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010316.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002551768.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
Likely benign
(Aug 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002545114.15
First in ClinVar: Jul 09, 2022 Last updated: Oct 08, 2024 |
Comment:
BRCA2: BP1, BS3:Supporting, BS1
Number of individuals with the variant: 10
|
|
Benign
(Sep 08, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531916.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
|
|
Benign
(Apr 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000494362.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
|
|
Likely benign
(Dec 18, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Vantari Genetics
Accession: SCV000267024.1
First in ClinVar: Apr 13, 2016 Last updated: Apr 13, 2016 |
|
|
Benign
(Nov 26, 2013)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167406.11
First in ClinVar: Jun 23, 2014 Last updated: Dec 02, 2017 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
|
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Benign
(Aug 15, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226714.5
First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018 |
Number of individuals with the variant: 6
Sex: mixed
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group D1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383778.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383777.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
Likely benign
(Sep 16, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000575734.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
|
|
Likely 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: SCV001139206.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002025842.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 4
Geographic origin: South Africa
|
|
Likely benign
(Feb 11, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683946.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
Benign
(Apr 17, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Study: Canadian Open Genetics Repository
Accession: SCV000219404.6 First in ClinVar: Mar 29, 2015 Last updated: Feb 04, 2024 |
|
|
Benign
(Feb 01, 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: SCV000073444.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
|
|
Benign
(Mar 05, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154080.2
First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022 |
|
|
Benign
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744534.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Uncertain significance
(Mar 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000538490.1
First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Clinvar: 10 labs classify as LB/Ben; ExAC: 0.2% (118/66734) European chromosomes (less)
Method: Genome/Exome Filtration
|
|
Benign
(Oct 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602845.7
First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024 |
|
|
Likely Benign
(Feb 05, 2024)
|
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: SCV004845611.1
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: 288
|
|
Benign
(Nov 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000196011.1
First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015 |
Tissue: Blood
|
|
Benign
(Aug 24, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743343.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799396.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Likely benign
(May 01, 2024)
|
no assertion criteria provided
Method: clinical testing
|
BRCA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805774.3
First in ClinVar: Feb 24, 2015 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).
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954450.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
probably not pathogenic
(Jul 13, 2012)
|
no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043228.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Likely benign.
Number of individuals with the variant: 1
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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|
Benign
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147282.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 36
Observation 2:
Number of individuals with the variant: 2
Geographic origin: Austria
Observation 3:
Number of individuals with the variant: 1
Geographic origin: Central/Eastern European
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Netherlands
Observation 5:
Number of individuals with the variant: 1
Geographic origin: Western European
Observation 6:
Number of individuals with the variant: 2
Ethnicity/Population group: Asian
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Spain
Observation 9:
Number of individuals with the variant: 7
Ethnicity/Population group: Central/Eastern European
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Central/Eastern European, Latin American
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Near Eastern Mid East
Observation 13:
Number of individuals with the variant: 49
Ethnicity/Population group: Western European
Observation 14:
Number of individuals with the variant: 3
Ethnicity/Population group: Western European, Ashkenazi
Observation 15:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Asian
Observation 16:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European
Observation 17:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, German, Irish
Observation 18:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
Observation 19:
Number of individuals with the variant: 1
Ethnicity/Population group: Western, Central/Eastern European
|
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Benign
(May 01, 2012)
|
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: SCV000115219.3
First in ClinVar: Feb 06, 2014 Last updated: Sep 27, 2014 |
|
|
Benign
(Nov 06, 2014)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: unknown
Allele origin:
germline
|
Pathway Genomics
Accession: SCV000207343.1
First in ClinVar: Feb 06, 2015 Last updated: Feb 06, 2015 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592175.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Ala2717Ser variant has been identified in five individuals from our laboratory, 36 times in the UMD-BRCA2 database and 112 times in the BIC database. … (more)
The p.Ala2717Ser variant has been identified in five individuals from our laboratory, 36 times in the UMD-BRCA2 database and 112 times in the BIC database. The variant was identified in 19 of 7810 proband chromosomes in individuals with breast, ovarian and prostate cancer patients (Edwards 2003, Diez 2003, Lubinski 2004, Salazar 2006, Giannini 2006, Soegaard 2008, Caux-Moncoutier 2009, Capanu 2011). However, an inadequate number of control chromosomes were tested to establish the variants frequency in the general population. This variant is listed in dbSNP database as coming from a "clinical source" (ID#: rs28897747) and was identified in more than one population with an average heterozygosity of 0.004+/-0.046, increasing the likelihood that this is a low frequency benign variant. The Ala2717 residue is not highly conserved in mammals and neither computational analyses (SIFT, AlignGVGD) nor other in silico protein modeling predictions (Karchin 2008, Spurdle 2008) suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. Finally, this variant was identified in at least three individuals in the UMD database who had a second premature truncating variant that is expected to be pathogenic, increasing the likelihood that the p.Ala2712Ser variant is not clinically significant. In summary, based on the above information this variant is classified as Benign. (less)
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Benign
(-)
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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: SCV000733313.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Likely benign
(Jan 05, 2018)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000787952.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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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: SCV001906396.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021 |
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Benign
(Mar 02, 2020)
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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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BRCAlab, Lund University
Accession: SCV004243802.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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Benign
(Oct 07, 2015)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000778717.2
First in ClinVar: Feb 24, 2015 Last updated: May 13, 2023 |
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Uncertain significance
(Feb 15, 2001)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863747.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084513.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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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Prevalence of Clinically Relevant Germline BRCA Variants in a Large Unselected South African Breast and Ovarian Cancer Cohort: A Public Sector Experience. | Van der Merwe NC | Frontiers in genetics | 2022 | DOI: 10.3389/fgene.2022.834265 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
Functional assays for analysis of variants of uncertain significance in BRCA2. | Guidugli L | Human mutation | 2014 | PMID: 24323938 |
Variants of uncertain significance in BRCA1 and BRCA2 assessment of in silico analysis and a proposal for communication in genetic counselling. | Moghadasi S | Journal of medical genetics | 2013 | PMID: 23231788 |
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 |
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). | Lindor NM | Human mutation | 2012 | PMID: 21990134 |
BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients. | Kote-Jarai Z | British journal of cancer | 2011 | PMID: 21952622 |
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes. | Hondow HL | BMC cancer | 2011 | PMID: 21702907 |
Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling. | Capanu M | Genetic epidemiology | 2011 | PMID: 21520273 |
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 |
Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. | Karchin R | Cancer informatics | 2008 | PMID: 19043619 |
BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. | Soegaard M | Clinical cancer research : an official journal of the American Association for Cancer Research | 2008 | PMID: 18559594 |
Clinical classification of BRCA1 and BRCA2 DNA sequence variants: the value of cytokeratin profiles and evolutionary analysis--a report from the kConFab Investigators. | Spurdle AB | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18375895 |
Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients. | Lee E | Breast cancer research : BCR | 2008 | PMID: 18284688 |
Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. | Simard J | Journal of medical genetics | 2007 | PMID: 16905680 |
BRCA1-2 mutations in breast cancer: identification of nine new variants of BRCA1-2 genes in a population from central Western Spain. | Salazar R | Cancer letters | 2006 | PMID: 15876480 |
Cancer variation associated with the position of the mutation in the BRCA2 gene. | Lubinski J | Familial cancer | 2004 | PMID: 15131399 |
Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. | Díez O | Human mutation | 2003 | PMID: 12955716 |
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 |
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. | Meindl A | International journal of cancer | 2002 | PMID: 11802209 |
Incidence of BRCA1/2 germ line alterations in a high risk cohort participating in a phase II chemoprevention trial. | Klemp J | European journal of cancer (Oxford, England : 1990) | 2000 | PMID: 10882858 |
http://evs.gs.washington.edu/EVS/; http://www.1000genomes.org/ | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
http://www.umd.be/BRCA2/ | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/85356a31-9019-465e-a963-2b1162997a9e | - | - | - | - |
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Text-mined citations for rs28897747 ...
HelpRecord last updated Oct 08, 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.