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NM_000059.4(BRCA2):c.2837A>T (p.Asp946Val) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 8, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003998698.2

Allele description [Variation Report for NM_000059.4(BRCA2):c.2837A>T (p.Asp946Val)]

NM_000059.4(BRCA2):c.2837A>T (p.Asp946Val)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.2837A>T (p.Asp946Val)
HGVS:
  • NC_000013.11:g.32337192A>T
  • NG_012772.3:g.26713A>T
  • NM_000059.4:c.2837A>TMANE SELECT
  • NP_000050.2:p.Asp946Val
  • NP_000050.3:p.Asp946Val
  • LRG_293t1:c.2837A>T
  • LRG_293:g.26713A>T
  • LRG_293p1:p.Asp946Val
  • NC_000013.10:g.32911329A>T
  • NM_000059.3:c.2837A>T
Protein change:
D946V
Links:
dbSNP: rs55972907
NCBI 1000 Genomes Browser:
rs55972907
Molecular consequence:
  • NM_000059.4:c.2837A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:
Breast-ovarian cancer, familial 2
Identifiers:
MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004832002All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jun 8, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select.

Niu Y, Ferreira Azevedo CA, Li X, Kamali E, Haagen Nielsen O, Storgaard Sørensen C, Frödin M.

Nat Genet. 2022 Dec;54(12):1983-1993. doi: 10.1038/s41588-022-01224-7. Epub 2022 Dec 5.

PubMed [citation]
PMID:
36471068
PMCID:
PMC9729100

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004832002.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces aspartic acid with valine at codon 946 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). A cell population-based knock-in assay functional study showed that this variant does not impact cell viability or response to PARP inhibitors (PMID: 36471068). To our knowledge, this variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024