ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3671G>T (p.Gly1224Val)

gnomAD frequency: 0.00001  dbSNP: rs587782670
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132093 SCV000187157 uncertain significance Hereditary cancer-predisposing syndrome 2014-04-27 criteria provided, single submitter clinical testing The p.G1224V variant (also known as c.3671G>T or 3899G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 3671. The glycine at codon 1224 is replaced by valine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project.To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 42000 alleles tested) in our clinical cohort (includes this individual).This amino acid position is highly 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 ofp.G1224Vremains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000703489 SCV000832392 uncertain significance Hereditary breast ovarian cancer syndrome 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1224 of the BRCA2 protein (p.Gly1224Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 142720). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health RCV000132093 SCV000906068 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985511 SCV001133769 uncertain significance not provided 2019-03-22 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000132093 SCV003846784 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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