ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.346G>A (p.Val116Ile) (rs753009349)

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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 RCV000564640 SCV000671939 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-05 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000588980 SCV000698098 uncertain significance not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.346G>A (p.Val116Ile) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 2/121256 control chromosomes at a frequency of 0.0000165, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; 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 RCV001055089 SCV001219457 uncertain significance Breast-ovarian cancer, familial 4 2019-12-01 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 116 of the RAD51D protein (p.Val116Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs753009349, ExAC 0.003%). This variant has not been reported in the literature in individuals with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 484770). 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.
Color RCV000564640 SCV001343600 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-12 criteria provided, single submitter clinical testing

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