ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.493C>G (p.Arg165Gly) (rs544654228)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115816 SCV000149725 uncertain significance not provided 2016-03-31 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.493C>G at the cDNA level, p.Arg165Gly (R165G) at the protein level, and results in the change of an Arginine to a Glycine (CGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Arg165Gly 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 Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51D Arg165Gly occurs at a position that is not conserved and is located in the ATPase domain (Kim 2011). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51D Arg165Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000524784 SCV000651753 uncertain significance Breast-ovarian cancer, familial 4 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 165 of the RAD51D protein (p.Arg165Gly). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 127890). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneKor MSA RCV000708749 SCV000822180 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000709439 SCV000839183 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000708749 SCV000908961 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-13 criteria provided, single submitter clinical testing

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