Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000478762 | SCV000572165 | uncertain significance | not provided | 2016-10-31 | criteria provided, single submitter | clinical testing | This variant is denoted RAD51D c.19G>C at the cDNA level, p.Gly7Arg (G7R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>CGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Gly7Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Gly7Arg occurs at a position where amino acids with properties similar to Glycine are tolerated across species and is located in the XRCC2 and single-stranded DNA binding domains (Miller 2004, Kim 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Gly7Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Labcorp Genetics |
RCV000816357 | SCV000956860 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-08-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 422649). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 7 of the RAD51D protein (p.Gly7Arg). This variant is not present in population databases (gnomAD no frequency). |