ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9904A>G (p.Arg3302Gly)

dbSNP: rs762935810
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222831 SCV000274571 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-18 criteria provided, single submitter clinical testing The p.R3302G variant (also known as c.9904A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 9904. The arginine at codon 3302 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly 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 RCV001853530 SCV002261868 uncertain significance Hereditary breast ovarian cancer syndrome 2021-06-16 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. This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230888). This variant is present in population databases (rs762935810, ExAC 0.001%). This sequence change replaces arginine with glycine at codon 3302 of the BRCA2 protein (p.Arg3302Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.
Color Diagnostics, LLC DBA Color Health RCV000222831 SCV004362846 uncertain significance Hereditary cancer-predisposing syndrome 2021-07-26 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 3302 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251230 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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.