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NM_000059.4(BRCA2):c.8663G>A (p.Arg2888His) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 6, 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:
RCV000113981.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.8663G>A (p.Arg2888His)]

NM_000059.4(BRCA2):c.8663G>A (p.Arg2888His)

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.8663G>A (p.Arg2888His)
Other names:
p.R2888H:CGT>CAT
HGVS:
  • NC_000013.11:g.32376700G>A
  • NG_012772.3:g.66221G>A
  • NM_000059.4:c.8663G>AMANE SELECT
  • NP_000050.2:p.Arg2888His
  • NP_000050.3:p.Arg2888His
  • LRG_293t1:c.8663G>A
  • LRG_293:g.66221G>A
  • LRG_293p1:p.Arg2888His
  • NC_000013.10:g.32950837G>A
  • NM_000059.3:c.8663G>A
  • U43746.1:n.8891G>A
Protein change:
R2888H
Links:
dbSNP: rs80359124
NCBI 1000 Genomes Browser:
rs80359124
Molecular consequence:
  • NM_000059.4:c.8663G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

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
SCV000147431Breast Cancer Information Core (BIC) (BRCA2)
no assertion criteria provided
Uncertain significance
(Sep 15, 2010) 		germlineclinical testing

SCV004846052All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Oct 6, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing
Polish Germangermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.

Kraus C, Hoyer J, Vasileiou G, Wunderle M, Lux MP, Fasching PA, Krumbiegel M, Uebe S, Reuter M, Beckmann MW, Reis A.

Int J Cancer. 2017 Jan 1;140(1):95-102. doi: 10.1002/ijc.30428. Epub 2016 Sep 23.

PubMed [citation]
PMID:
27616075

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]
PMID:
30287823
PMCID:
PMC6172276
See all PubMed Citations (6)

Details of each submission

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147431.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Polish German1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004846052.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (6)

Description

This missense variant replaces arginine with histidine at codon 2888 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 an individual affected with breast cancer (PMID: 27616075) and in a breast cancer case-control meta-analysis in 3/60463 cases and 1/53460 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_006568). This variant also has been reported in three Japanese case-control studies on breast, pancreatic and prostate cancer, in which this variant was detected in one unaffected individual per study and was absent in cancer cases (PMID: 30287823, 31214711, 32980694). This variant has been identified in 3/282684 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: Oct 20, 2024