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NM_000059.4(BRCA2):c.4372C>T (p.His1458Tyr) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:
Uncertain significance (3 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:
RCV000077323.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.4372C>T (p.His1458Tyr)]

NM_000059.4(BRCA2):c.4372C>T (p.His1458Tyr)

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.4372C>T (p.His1458Tyr)
HGVS:
  • NC_000013.11:g.32338727C>T
  • NG_012772.3:g.28248C>T
  • NM_000059.4:c.4372C>TMANE SELECT
  • NP_000050.2:p.His1458Tyr
  • NP_000050.3:p.His1458Tyr
  • LRG_293t1:c.4372C>T
  • LRG_293:g.28248C>T
  • LRG_293p1:p.His1458Tyr
  • NC_000013.10:g.32912864C>T
  • NM_000059.3:c.4372C>T
  • U43746.1:n.4600C>T
Nucleotide change:
4600C>T
Protein change:
H1458Y
Links:
dbSNP: rs80358672
NCBI 1000 Genomes Browser:
rs80358672
Molecular consequence:
  • NM_000059.4:c.4372C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

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
SCV000109120Sharing Clinical Reports Project (SCRP)
no assertion criteria provided
Uncertain significance
(Mar 18, 2010) 		germlineclinical testing

SCV000146414Breast Cancer Information Core (BIC) (BRCA2)
no assertion criteria provided
Uncertain significance
(Dec 23, 2003) 		germlineclinical testing

SCV004845674All of Us Research Program, National Institutes of Health
criteria provided, single submitter

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

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided1not providednot provided1not providedclinical testing
not providedgermlineunknown1not providednot provided108544not providedclinical testing
Asiangermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases.

Anwar SL, Haryono SJ, Aryandono T, Datasena IG.

Asian Pac J Cancer Prev. 2016;17(4):1987-91.

PubMed [citation]
PMID:
27221885

Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls.

Momozawa Y, Iwasaki Y, Hirata M, Liu X, Kamatani Y, Takahashi A, Sugano K, Yoshida T, Murakami Y, Matsuda K, Nakagawa H, Spurdle AB, Kubo M.

J Natl Cancer Inst. 2020 Apr 1;112(4):369-376. doi: 10.1093/jnci/djz124.

PubMed [citation]
PMID:
31214711
PMCID:
PMC7156928
See all PubMed Citations (4)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000109120.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot provided1not providednot providednot providednot providednot providednot provided

From Breast Cancer Information Core (BIC) (BRCA2), SCV000146414.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Asian1not 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, SCV004845674.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (4)

Description

This missense variant replaces histidine with tyrosine at codon 1458 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 and an individual affected with prostate cancer (PMID: 27221885, 31214711). In a large breast cancer case-control meta analysis conducted by the BRIDGES consortium, this variant was reported in 2/60466 cases and 3/53461 unaffected controls (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_001673). This variant has been identified in 7/275926 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 provided1not providednot providednot provided

Last Updated: Jun 2, 2024