ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.496A>G (p.Arg166Gly) (rs1064793246)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483552 SCV000565468 uncertain significance not provided 2015-01-30 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.496A>G at the cDNA level, p.Arg166Gly (R166G) at the protein level, and results in the change of an Arginine to a Glycine (AGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Arg166Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Arg166Gly occurs at a position that is highly conserved across species and is located in the ATPase domain (Kim 2011). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether RAD51D Arg166Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000541623 SCV000651754 uncertain significance Breast-ovarian cancer, familial 4 2017-04-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 166 of the RAD51D protein (p.Arg166Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RAD51D-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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