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NM_000059.4(BRCA2):c.7970A>C (p.Lys2657Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 5, 2022
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:
RCV000509666.4

Allele description [Variation Report for NM_000059.4(BRCA2):c.7970A>C (p.Lys2657Thr)]

NM_000059.4(BRCA2):c.7970A>C (p.Lys2657Thr)

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.7970A>C (p.Lys2657Thr)
HGVS:
  • NC_000013.11:g.32362687A>C
  • NG_012772.3:g.52208A>C
  • NM_000059.4:c.7970A>CMANE SELECT
  • NP_000050.2:p.Lys2657Thr
  • NP_000050.3:p.Lys2657Thr
  • LRG_293t1:c.7970A>C
  • LRG_293:g.52208A>C
  • LRG_293p1:p.Lys2657Thr
  • NC_000013.10:g.32936824A>C
  • NM_000059.3:c.7970A>C
Protein change:
K2657T
Links:
dbSNP: rs1555286874
NCBI 1000 Genomes Browser:
rs1555286874
Molecular consequence:
  • NM_000059.4:c.7970A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000607826Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jan 5, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Strong functional data for pathogenicity or neutrality classify BRCA2 DNA-binding-domain variants of uncertain significance.

Richardson ME, Hu C, Lee KY, LaDuca H, Fulk K, Durda KM, Deckman AM, Goldgar DE, Monteiro ANA, Gnanaolivu R, Hart SN, Polley EC, Chao E, Pesaran T, Couch FJ.

Am J Hum Genet. 2021 Mar 4;108(3):458-468. doi: 10.1016/j.ajhg.2021.02.005. Epub 2021 Feb 19.

PubMed [citation]
PMID:
33609447
PMCID:
PMC8008494

Details of each submission

From Ambry Genetics, SCV000607826.5

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

Description

The p.K2657T variant (also known as c.7970A>C), located in coding exon 16 of the BRCA2 gene, results from an A to C substitution at nucleotide position 7970. The lysine at codon 2657 is replaced by threonine, an amino acid with similar properties. This variant was non-functional in a homology-directed DNA repair (HDR) assay (Ambry internal data). This alteration is also predicted to destabilize the local structure and disrupt the protein binding ability of BRCA2 (Yang H et al. Science 2002 Sep;297:1837-48; Marston NJ et al. Mol. Cell. Biol. 1999 Jul;19:4633-42; Ambry internal data) This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Sep 29, 2024