ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.8567A>C (p.Glu2856Ala)
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.
Uncertain significance(1); Benign(13); Likely benign(13)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.8567A>C (p.Glu2856Ala)
Variation ID: 38168 Accession: VCV000038168.88
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32371035 (GRCh38) [ NCBI UCSC ] 13: 32945172 (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 May 1, 2024 Feb 5, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000059.4:c.8567A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Glu2856Ala missense NC_000013.11:g.32371035A>C NC_000013.10:g.32945172A>C NG_012772.3:g.60556A>C LRG_293:g.60556A>C LRG_293t1:c.8567A>C LRG_293p1:p.Glu2856Ala NP_000050.2:p.Glu2856Ala U43746.1:n.8795A>C - Protein change
- E2856A
- Other names
- p.E2856A:GAG>GCG
- NP_000050.3:p.Glu2856Ala
- 8795A>C
- Canonical SPDI
- NC_000013.11:32371034:A:C
-
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 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
Exome Aggregation Consortium (ExAC) 0.00088
The Genome Aggregation Database (gnomAD), exomes 0.00107
Trans-Omics for Precision Medicine (TOPMed) 0.00124
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00146
The Genome Aggregation Database (gnomAD) 0.00158
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 |
18723 | 18881 |
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/Likely benign (12) |
criteria provided, multiple submitters, no conflicts
|
Feb 5, 2024 | RCV000031751.30 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000034464.46 | |
Conflicting interpretations of pathogenicity (9) |
criteria provided, conflicting classifications
|
Aug 15, 2023 | RCV000152885.40 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Oct 19, 2020 | RCV000131022.19 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000167825.27 | |
Likely benign (1) |
criteria provided, single submitter
|
Feb 28, 2018 | RCV000371112.13 | |
Likely benign (2) |
criteria provided, single submitter
|
Mar 8, 2023 | RCV000735613.14 |
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
(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: SCV000196016.1
First in ClinVar: May 27, 2015 Last updated: May 27, 2015 |
Tissue: Blood
|
|
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: SCV000538491.1
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: 0.1% (94/66682) European chromosomes (less)
Method: Genome/Exome Filtration
|
|
Likely benign
(Sep 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002070567.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
Benign
(Oct 19, 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: SCV000602794.8
First in ClinVar: Sep 28, 2017 Last updated: Feb 20, 2024 |
|
|
Benign
(Nov 19, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000185950.7
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
(Aug 25, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805782.1
First in ClinVar: Feb 24, 2015 Last updated: Feb 24, 2015 |
|
|
Likely 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: SCV002025857.2
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 2
Geographic origin: South Africa
|
|
Benign
(Sep 29, 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: SCV000494364.2
First in ClinVar: Feb 04, 2017 Last updated: Dec 11, 2022 |
|
|
Likely benign
(Nov 25, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683983.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
Benign
(Sep 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761833.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
|
|
Likely benign
(Apr 08, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000154095.2
First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022 |
|
|
Likely benign
(Mar 08, 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
Accession: SCV000219411.7
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
|
Invitae
Accession: SCV000073571.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 28, 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: SCV004846043.1
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: 386
|
|
Likely benign
(Apr 25, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000267847.1
First in ClinVar: Jan 31, 2016 Last updated: Jan 31, 2016 |
|
|
Benign
(Apr 19, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586982.1 First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
|
|
Benign
(Jan 07, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000167412.11
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)
|
|
Benign
(Oct 09, 2014)
|
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: SCV000743349.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
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: SCV000744542.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
Likely benign
(May 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000747808.2
First in ClinVar: May 03, 2018 Last updated: Jul 27, 2018 |
|
|
Likely benign
(May 01, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000202304.7
First in ClinVar: Jan 29, 2015 Last updated: Dec 02, 2017 |
Number of individuals with the variant: 2
Sex: mixed
|
|
Likely benign
(Feb 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group D1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383788.3
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
(Feb 28, 2018)
|
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: SCV000383789.3
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)
|
|
Benign
(Oct 19, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002531958.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 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: SCV002010305.3
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: SCV002551827.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
Likely benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001148998.21
First in ClinVar: Feb 03, 2020 Last updated: Apr 15, 2024 |
Comment:
BRCA2: BP4
Number of individuals with the variant: 16
|
|
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: SCV000147403.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 56
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Austria
Observation 3:
Number of individuals with the variant: 2
Geographic origin: Central/Eastern European
Observation 4:
Number of individuals with the variant: 1
Geographic origin: Germany
Observation 5:
Number of individuals with the variant: 1
Geographic origin: Ireland, Welsh, English, Germany
Observation 6:
Number of individuals with the variant: 1
Geographic origin: Near Eastern Mid East
Observation 7:
Number of individuals with the variant: 1
Geographic origin: Scandinavian, English, Norway, France
Observation 8:
Number of individuals with the variant: 5
Geographic origin: Western European
Observation 9:
Number of individuals with the variant: 1
Ethnicity/Population group: African
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Ashkenazi
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Germany
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Italy
Observation 14:
Number of individuals with the variant: 10
Ethnicity/Population group: Central/Eastern European
Observation 15:
Number of individuals with the variant: 2
Ethnicity/Population group: Native American
Observation 16:
Number of individuals with the variant: 94
Ethnicity/Population group: Western European
Observation 17:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European
Observation 18:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Central/Eastern European, French Canadian
Observation 19:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Irish
Observation 20:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Italian
Observation 21:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
Observation 22:
Number of individuals with the variant: 2
Ethnicity/Population group: Western Europeanan, Central/Eastern European
|
|
Likely 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: SCV000207353.1
First in ClinVar: Feb 06, 2015 Last updated: Feb 06, 2015 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733319.1 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: SCV001800804.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
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: SCV001951665.1 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: SCV000043231.1 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)
|
|
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: SCV000054359.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014 |
|
|
Likely benign
(Aug 14, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
True Health Diagnostics
Accession: SCV000787955.1
First in ClinVar: Jul 27, 2018 Last updated: Jul 27, 2018 |
|
|
Uncertain significance
(Aug 16, 2001)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000863751.1 First in ClinVar: Dec 24, 2018 Last updated: Dec 24, 2018 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
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: SCV000592209.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Glu2856Ala variant is identified in the literature in 26 out of 7714 proband chromosomes (frequency 0.003) with breast, ovarian and prostate cancers, however it … (more)
The p.Glu2856Ala variant is identified in the literature in 26 out of 7714 proband chromosomes (frequency 0.003) with breast, ovarian and prostate cancers, however it is also identified in 16 out of 5286 control chromosomes (frequency 0.003) (Spitzer 2000, Borg 2010, Soegaard 2008, Edwards 2003, Chenevix-Trench 2006, Evans 2008), and listed in dbSNP database as coming from a "clinical source" (ID#: rs11571747) with an average heterozygosity of 0.002+/-0.031 in various human populations, therefore increasing the likelihood of this variant to be benign. In the UMD database, this variant has been identified in two (out of 23) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, and also found in an breast cancer individual in the homozygous state (Chenevix-Trench 2006), further suggesting the benign nature of this variant. The p.Glu2856 residue is conserved in mammals and computational analyses (PolyPhen2, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein, leaning more towards deleterious, but this information is not predictive enough to assume pathogenicity. Furthermore, Myriad genetics has reported this variant as a polymorphism increasing the likelihood this variant is benign (personal communication). Based on the above information, this variant is classified as Benign. (less)
Number of individuals with the variant: 2
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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: SCV001906421.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 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: SCV004243827.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
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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 |
A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity. | Guidugli L | Cancer research | 2013 | PMID: 23108138 |
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 |
Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. | Karchin R | Cancer informatics | 2008 | PMID: 19043619 |
Clinically applicable models to characterize BRCA1 and BRCA2 variants of uncertain significance. | Spearman AD | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2008 | PMID: 18824701 |
Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2. | Kuznetsov SG | Nature medicine | 2008 | PMID: 18607349 |
Colocalisation of predicted exonic splicing enhancers in BRCA2 with reported sequence variants. | Pettigrew CA | Breast cancer research and treatment | 2008 | PMID: 17899372 |
Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. | Johnson N | Human molecular genetics | 2007 | PMID: 17341484 |
Genetic and histopathologic evaluation of BRCA1 and BRCA2 DNA sequence variants of unknown clinical significance. | Chenevix-Trench G | Cancer research | 2006 | PMID: 16489001 |
BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian breast/ovarian cancer families. | Claes K | British journal of cancer | 2004 | PMID: 15026808 |
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 |
The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. | Malone KE | Cancer | 2000 | PMID: 10717622 |
Detection of BRCA1 and BRCA2 mutations in breast cancer families by a comprehensive two-stage screening procedure. | Spitzer E | International journal of cancer | 2000 | PMID: 10699917 |
A rapid method for identification of Mycobacterium species by polyacrylamide gel electrophoresis of soluble cell proteins. | De Jong A | Journal of medical microbiology | 1991 | PMID: 1990134 |
http://evs.gs.washington.edu/EVS/; http://www.1000genomes.org/ | - | - | - | - |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 | - | - | - | - |
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Text-mined citations for rs11571747 ...
HelpRecord last updated May 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.