ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.292T>A (p.Tyr98Asn) (rs730881946)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222222 SCV000276514 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000222222 SCV000686441 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-12 criteria provided, single submitter clinical testing
GeneDx RCV000160944 SCV000211651 uncertain significance not provided 2018-10-12 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.292T>A at the cDNA level, p.Tyr98Asn (Y98N) at the protein level, and results in the change of a Tyrosine to an Asparagine (TAT>AAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Tyr98Asn 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 Tyr98Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000780676 SCV000918136 uncertain significance not specified 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.292T>A (p.Tyr98Asn) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 1/246174 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000537449 SCV000651728 uncertain significance Breast-ovarian cancer, familial 4 2017-05-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with asparagine at codon 98 of the RAD51D protein (p.Tyr98Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 182855). 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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