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NM_000059.4(BRCA2):c.8350C>T (p.Arg2784Trp) AND BRCA2-related condition

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 10, 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:
RCV003390705.4

Allele description

NM_000059.4(BRCA2):c.8350C>T (p.Arg2784Trp)

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.8350C>T (p.Arg2784Trp)
HGVS:
  • NC_000013.11:g.32370420C>T
  • NG_012772.3:g.59941C>T
  • NM_000059.4:c.8350C>TMANE SELECT
  • NP_000050.2:p.Arg2784Trp
  • NP_000050.3:p.Arg2784Trp
  • LRG_293t1:c.8350C>T
  • LRG_293:g.59941C>T
  • LRG_293p1:p.Arg2784Trp
  • NC_000013.10:g.32944557C>T
  • NM_000059.3:c.8350C>T
  • U43746.1:n.8578C>T
  • p.Arg2784Trp
  • p.R2784W
Nucleotide change:
8578C>T
Protein change:
R2784W
Links:
dbSNP: rs80359075
NCBI 1000 Genomes Browser:
rs80359075
Molecular consequence:
  • NM_000059.4:c.8350C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
BRCA2-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004118990PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jul 10, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 PreventionGenetics, part of Exact Sciences, SCV004118990.1

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

Description

The BRCA2 c.8350C>T variant is predicted to result in the amino acid substitution p.Arg2784Trp. This variant has been reported in an individual with triple-negative breast cancer (Table S4, Kraus et al. 2017. PubMed ID: 27616075), multiple families with a history of hereditary breast and/or ovarian cancer (HBOC) (van der Hout et al. 2006. PubMed ID: 16683254; Gómez García et al. 2009. PubMed ID: 19200354; Table S3, Casadei et al. 2019. PubMed ID: 31843900; Table S2, Shao et al. 2020. PubMed ID: 31742824), and in a non-smoking woman with lung adenocarcinoma (Donner et al. 2018. PubMed ID: 30032850). It has also been observed in an ovarian tumor (Additional file 4, Da Costa et al. 2019. PubMed ID: 31060523). Experimental studies have demonstrated that this variant reduces homology-directed DNA repair (HRD) (Table 2, Guidugli et al. 2013. PubMed ID: 23108138; Farrugia et al. 2008. PubMed ID: 18451181; Guidugli et al. 2018. PubMed ID: 29394989; Mesman et al. 2019. PubMed ID: 29988080). Recent studies have interpreted this variant as pathogenic based on HRD assay results (Hart et al. 2019. PubMed ID: 29884841). This variant has been reported in the gnomAD public population database in 2 of ~251,000 alleles (https://gnomad.broadinstitute.org/variant/13-32944557-C-T) and is interpreted as likely pathogenic by the vast majority of clinical laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/38155/). An internal summary of amino acid substitution prediction programs predicts the p.Arg2784Trp change to be “damaging” (Liu et al. 2016. PMID: 26555599). This variant is interpreted as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024