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NM_000059.4(BRCA2):c.7682A>C (p.Gln2561Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 15, 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:
RCV004035576.1

Allele description [Variation Report for NM_000059.4(BRCA2):c.7682A>C (p.Gln2561Pro)]

NM_000059.4(BRCA2):c.7682A>C (p.Gln2561Pro)

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.7682A>C (p.Gln2561Pro)
HGVS:
  • NC_000013.11:g.32357806A>C
  • NG_012772.3:g.47327A>C
  • NM_000059.4:c.7682A>CMANE SELECT
  • NP_000050.3:p.Gln2561Pro
  • LRG_293t1:c.7682A>C
  • LRG_293:g.47327A>C
  • NC_000013.10:g.32931943A>C
  • NM_000059.3:c.7682A>C
Protein change:
Q2561P
Links:
dbSNP: rs55647716
NCBI 1000 Genomes Browser:
rs55647716
Molecular consequence:
  • NM_000059.4:c.7682A>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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005029997Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Sep 15, 2023) 		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, SCV005029997.1

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

Description

The p.Q2561P variant (also known as c.7682A>C), located in coding exon 15 of the BRCA2 gene, results from an A to C substitution at nucleotide position 7682. The glutamine at codon 2561 is replaced by proline, an amino acid with similar properties. This variant was non-functional in a homology-directed DNA repair (HDR) assay (Richardson ME et al. Am J Hum Genet, 2021 Mar;108:458-468). An internal structural analysis indicates that this variant is disruptive to the protein (Ambry internal data). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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