ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6313A>G (p.Ile2105Val)

dbSNP: rs397507368
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000637370 SCV000758826 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-05 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. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2105 of the BRCA2 protein (p.Ile2105Val). This variant is present in population databases (rs397507368, gnomAD 0.006%). 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: 38034). 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. Studies have shown that this missense change does not affect mRNA splicing (PMID: 29280214).
Ambry Genetics RCV001025126 SCV001187255 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-15 criteria provided, single submitter clinical testing The p.I2105V variant (also known as c.6313A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6313. The isoleucine at codon 2105 is replaced by valine, 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001025126 SCV003852416 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).
Sharing Clinical Reports Project (SCRP) RCV000031616 SCV000054223 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2006-11-09 no assertion criteria provided clinical testing

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.