ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.164G>A (p.Arg55Gln) (rs151198586)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217170 SCV000273742 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000217170 SCV000537563 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000235863 SCV000294069 uncertain significance not provided 2018-10-15 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.164G>A at the cDNA level, p.Arg55Gln (R55Q) 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 a pathogenic or benign germline variant. RAD51D Arg55Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). RAD51D Arg55Gln is located within the XRCC2 and the ssDNA binding domains (Miller 2004, Kim 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure or function. Based on currently available evidence, it is unclear whether RAD51D Arg55Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GeneKor MSA RCV000217170 SCV000822175 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Invitae RCV000459023 SCV000551357 uncertain significance Breast-ovarian cancer, familial 4 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 55 of the RAD51D protein (p.Arg55Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs151198586, ExAC 0.01%). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 230266). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Mendelics RCV000709451 SCV000839195 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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