Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000059.3(BRCA2):c.8057T>C (p.Leu2686Pro)

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 5, 2020
Accession:
VCV000052489.8
Variation ID:
52489
Description:
single nucleotide variant
Help

NM_000059.3(BRCA2):c.8057T>C (p.Leu2686Pro)

Allele ID
67157
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q13.1
Genomic location
13: 32363259 (GRCh38) GRCh38 UCSC
13: 32937396 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.10:g.32937396T>C
NC_000013.11:g.32363259T>C
NM_000059.3:c.8057T>C NP_000050.2:p.Leu2686Pro missense
... more HGVS
Protein change
L2686P
Other names
-
Canonical SPDI
NC_000013.11:32363258:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA025427
dbSNP: rs28897746
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Dec 10, 2017 RCV000479056.1
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Jan 22, 2020 RCV000568548.4
Likely pathogenic 3 criteria provided, multiple submitters, no conflicts Oct 5, 2020 RCV001264563.3
Uncertain significance 1 no assertion criteria provided Feb 20, 2004 RCV000113861.1
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
14102 14215

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 10, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000883517.1
Submitted: (Oct 10, 2018)
Evidence details
Likely pathogenic
(Oct 08, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV001340336.1
Submitted: (May 19, 2020)
Comment:
This missense variant replaces leucine with proline at codon 2686 of the BRCA2 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
Evidence details
Likely pathogenic
(Oct 05, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001442781.1
Submitted: (Nov 10, 2020)
Evidence details
Publications
PubMed (8)
Comment:
Variant summary: BRCA2 c.8057T>C (p.Leu2686Pro) results in a non-conservative amino acid change located in the BRCA2, OB1 domain (IPR015187) of the encoded protein sequence. Five … (more)
Likely pathogenic
(Oct 10, 2018)
criteria provided, single submitter
Method: curation
Hereditary Breast and Ovarian Cancer
Allele origin: germline
Cancer Variant Interpretation Group UK, Institute of Cancer Research, London
Accession: SCV001478294.1
Submitted: (Dec 17, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Data used in classification: The frequency of this variant is 0/138,632 individuals (gnomAD) (PM2_mod). This variant is predicted deleterious on AlignGVGD (class: C65), SIFT (Deleterious), … (more)
Likely pathogenic
(Sep 24, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV001574246.1
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces leucine with proline at codon 2686 of the BRCA2 protein (p.Leu2686Pro). The leucine residue is highly conserved and there is a … (more)
Likely pathogenic
(May 19, 2016)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565756.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted BRCA2 c.8057T>C at the cDNA level, p.Leu2686Pro (L2686P) at the protein level, and results in the change of a Leucine to … (more)
Pathogenic
(Jan 22, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000666009.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (8)
Comment:
The p.L2686P pathogenic mutation (also known as c.8057T>C), located in coding exon 17 of the BRCA2 gene, results from a T to C substitution at … (more)
Uncertain significance
(Feb 20, 2004)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 2
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000147259.1
Submitted: (Mar 28, 2014)
Evidence details

Functional evidence

Help
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 this variant

Help
Title Author Journal Year Link
The functional impact of variants of uncertain significance in BRCA2. Mesman RLS Genetics in medicine : official journal of the American College of Medical Genetics 2019 PMID: 29988080
Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models. Hart SN Genetics in medicine : official journal of the American College of Medical Genetics 2019 PMID: 29884841
Assessment of the Clinical Relevance of BRCA2 Missense Variants by Functional and Computational Approaches. Guidugli L American journal of human genetics 2018 PMID: 29394989
Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study. Azzollini J European journal of internal medicine 2016 PMID: 27062684
Biallelic FANCD1/BRCA2 mutations predisposing to glioblastoma multiforme with multiple oncogenic amplifications. Dodgshun AJ Cancer genetics 2016 PMID: 26740091
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Houdayer C Human mutation 2012 PMID: 22505045
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
Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. Karchin R Cancer informatics 2008 PMID: 19043619
Computational and structural investigation of deleterious functional SNPs in breast cancer BRCA2 gene. Rajasekaran R Sheng wu gong cheng xue bao = Chinese journal of biotechnology 2008 PMID: 18724707
The breast cancer information core: database design, structure, and scope. Szabo C Human mutation 2000 PMID: 10923033

Text-mined citations for rs28897746...

Help
These 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 Jun 14, 2021