ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2456A>G (p.Gln819Arg)

dbSNP: rs1555282683
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561854 SCV000666165 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-10 criteria provided, single submitter clinical testing The p.Q819R variant (also known as c.2456A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2456. The glutamine at codon 819 is replaced by arginine, an amino acid with highly similar properties. This alteration was observed with an allele frequency of 0.00014 in 7,051 unselected female breast cancer patients and was observed with an allele frequency of 0.0000 in 11,241 female controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083).This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001858186 SCV002252849 uncertain significance Hereditary breast ovarian cancer syndrome 2023-05-31 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 481611). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 819 of the BRCA2 protein (p.Gln819Arg).
University of Washington Department of Laboratory Medicine, University of Washington RCV000561854 SCV003848332 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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