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NM_000059.4(BRCA2):c.464G>C (p.Arg155Thr) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 13, 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:
RCV000031497.8

Allele description [Variation Report for NM_000059.4(BRCA2):c.464G>C (p.Arg155Thr)]

NM_000059.4(BRCA2):c.464G>C (p.Arg155Thr)

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.464G>C (p.Arg155Thr)
Other names:
R115T; p.R155T:AGA>ACA
HGVS:
  • NC_000013.11:g.32326139G>C
  • NG_012772.3:g.15660G>C
  • NM_000059.4:c.464G>CMANE SELECT
  • NP_000050.2:p.Arg155Thr
  • NP_000050.3:p.Arg155Thr
  • LRG_293t1:c.464G>C
  • LRG_293:g.15660G>C
  • LRG_293p1:p.Arg155Thr
  • NC_000013.10:g.32900276G>C
  • NM_000059.3:c.464G>C
Nucleotide change:
692G>C
Protein change:
R155T
Links:
dbSNP: rs377639990
NCBI 1000 Genomes Browser:
rs377639990
Molecular consequence:
  • NM_000059.4:c.464G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
5

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
SCV000054102Sharing Clinical Reports Project (SCRP)
no assertion criteria provided
Uncertain significance
(May 5, 2010) 		germlineclinical testing

SCV004846782All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided2not providednot provided2not providedclinical testing
not providedgermlineunknown3not providednot provided108544not providedclinical testing

Citations

PubMed

Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome.

Santonocito C, Rizza R, Paris I, Marchis L, Paolillo C, Tiberi G, Scambia G, Capoluongo E.

Cancers (Basel). 2020 May 19;12(5). doi:pii: E1286. 10.3390/cancers12051286.

PubMed [citation]
PMID:
32438681
PMCID:
PMC7281099

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]
PMID:
33471991
PMCID:
PMC7611105
See all PubMed Citations (5)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054102.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot provided2not providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004846782.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (5)

Description

This missense variant replaces arginine with threonine at codon 155 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals with a personal and/or family history of breast or ovarian cancer (PMID: 32438681, 34178674, 34572941). An individual affected with breast cancer carried both this variant and a pathogenic BRCA1 co-variant (PMID: 32438681). This variant also has been reported in a breast cancer case-control meta-analysis in 1/53460 unaffected individuals and absent in 60466 cases (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_007554). This variant has been identified in 1/251052 chromosomes 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 provided3not providednot providednot provided

Last Updated: Sep 29, 2024