ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.910G>T (p.Gly304Cys) (rs759392029)

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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 RCV000219168 SCV000276628 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000219168 SCV000686500 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781800 SCV000920130 uncertain significance not specified 2018-08-17 criteria provided, single submitter clinical testing Variant summary: RAD51D c.910G>T (p.Gly304Cys) results in a non-conservative amino acid change located in the DNA recombination and repair protein Rad51-like, C-terminal and AAA+ ATPase domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246252 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.910G>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000460833 SCV000551337 uncertain significance Breast-ovarian cancer, familial 4 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 304 of the RAD51D protein (p.Gly304Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. 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: 232482). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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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