ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.5G>C (p.Gly2Ala) (rs763716638)

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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 RCV000574423 SCV000663823 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000574423 SCV000686472 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588399 SCV000698109 uncertain significance not provided 2017-08-16 criteria provided, single submitter clinical testing Variant summary: The c.5G>C (p.Gly2Ala) in RAD51D gene is a missense variant involves a non-conserved nucleotide and 3/5 in silico tools predict benign outcome. The variant is located outside of any known functional domain or repeat, however no functional studies confirming no effect of this change on the protein function were published at the time of evaluation. The variant is present at a low frequencies in the control population datasets of ExAC and gnomAD (2.201e-5; 1/119274 and 6/272552chrs tested, respectively). These frequencies do not exceed the maximal expected allele frequency for a disease causing allele in RAD51D gene (0.000125). The variant has been not, to our knowledge, been reported in affected individuals via published reports or cited by reputable databases/clinical. Taken together, the variant was classified as VUS, until new information becomes available.
Invitae RCV000649698 SCV000771530 uncertain significance Breast-ovarian cancer, familial 4 2018-07-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 2 of the RAD51D protein (p.Gly2Ala). The glycine residue is weakly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs763716638, ExAC 0.009%). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 480530). 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.

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