ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3650G>A (p.Arg1217Lys)

gnomAD frequency: 0.00001  dbSNP: rs1306577496
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985509 SCV001133767 uncertain significance not provided 2019-06-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020805 SCV001182335 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-25 criteria provided, single submitter clinical testing The p.R1217K variant (also known as c.3650G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 3650. The arginine at codon 1217 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001359613 SCV001555488 uncertain significance Hereditary breast ovarian cancer syndrome 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1217 of the BRCA2 protein (p.Arg1217Lys). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 801104). 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 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001020805 SCV003846763 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.