ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6644A>G (p.Tyr2215Cys)

dbSNP: rs753615126
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 RCV001284579 SCV001470437 uncertain significance not provided 2020-03-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002366105 SCV002663236 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-27 criteria provided, single submitter clinical testing The p.Y2215C variant (also known as c.6644A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6644. The tyrosine at codon 2215 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002366105 SCV003847330 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV003645226 SCV004532596 uncertain significance Hereditary breast ovarian cancer syndrome 2024-08-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2215 of the BRCA2 protein (p.Tyr2215Cys). This variant is present in population databases (rs753615126, 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: 993209). 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.

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.