NM_000059.3(BRCA2):c.7975A>G (p.Arg2659Gly) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Nov 18, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001325838.1

Allele description [Variation Report for NM_000059.3(BRCA2):c.7975A>G (p.Arg2659Gly)]

NM_000059.3(BRCA2):c.7975A>G (p.Arg2659Gly)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.7975A>G (p.Arg2659Gly)
HGVS:
  • NC_000013.11:g.32362692A>G
  • NG_012772.3:g.52213A>G
  • NM_000059.3:c.7975A>G
  • NP_000050.2:p.Arg2659Gly
  • LRG_293t1:c.7975A>G
  • LRG_293:g.52213A>G
  • LRG_293p1:p.Arg2659Gly
  • NC_000013.10:g.32936829A>G
  • NM_000059.4:c.7975A>GMANE SELECT
  • U43746.1:n.8203A>G
Nucleotide change:
8203A>G
Protein change:
R2659G
Links:
dbSNP: rs80359026
NCBI 1000 Genomes Browser:
rs80359026
Molecular consequence:
  • NM_000059.3:c.7975A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001516845Invitaecriteria provided, single submitter
Uncertain significance
(Nov 18, 2018)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

EMMA, a cost- and time-effective diagnostic method for simultaneous detection of point mutations and large-scale genomic rearrangements: application to BRCA1 and BRCA2 in 1,525 patients.

Caux-Moncoutier V, Castéra L, Tirapo C, Michaux D, Rémon MA, Laugé A, Rouleau E, De Pauw A, Buecher B, Gauthier-Villars M, Viovy JL, Stoppa-Lyonnet D, Houdayer C.

Hum Mutat. 2011 Mar;32(3):325-34. doi: 10.1002/humu.21414. Epub 2011 Feb 8.

PubMed [citation]
PMID:
21120943

Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity.

Pinto P, Paulo P, Santos C, Rocha P, Pinto C, Veiga I, Pinheiro M, Peixoto A, Teixeira MR.

Breast Cancer Res Treat. 2016 Sep;159(2):245-56. doi: 10.1007/s10549-016-3948-z. Epub 2016 Aug 23.

PubMed [citation]
PMID:
27553368
See all PubMed Citations (11)

Details of each submission

From Invitae, SCV001516845.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

This sequence change replaces arginine with glycine at codon 2659 of the BRCA2 protein (p.Arg2659Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with breast and/or ovarian cancer in the literature (PMID: 21120943, 27553368, 29335924, 30254663). This variant is also known as c.8204G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 38130). Experimental studies have shown that this change results in partial aberrant splicing and production of low amounts of an alternate transcript lacking exon 17 in addition to wild-type transcript (PMID: 22505045, 12624152, 28339459). In vitro functional analysis showed this change results in impaired homologous repair activity compared to wild-type BRCA2 protein (PMID: 15695382, 23108138, 29884841). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 23, 2021

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