ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.824G>A (p.Arg275Gln) (rs368914740)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165258 SCV000215974 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000165258 SCV000686491 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-26 criteria provided, single submitter clinical testing
GeneDx RCV000235620 SCV000293084 uncertain significance not provided 2018-10-16 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.824G>A at the cDNA level, p.Arg275Gln (R275Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Arg275Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the RAD51C binding domain (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51D Arg275Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000470966 SCV000551324 uncertain significance Breast-ovarian cancer, familial 4 2018-10-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 275 of the RAD51D protein (p.Arg275Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. 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: 185774). 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 disruptive, 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.

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