ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.53A>G (p.Gln18Arg) (rs546225564)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219745 SCV000276694 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-14 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence
Counsyl RCV000409529 SCV000489638 uncertain significance Breast-ovarian cancer, familial 4 2016-11-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507009 SCV000602160 uncertain significance not specified 2017-01-17 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760065 SCV000889826 uncertain significance not provided 2018-01-09 criteria provided, single submitter clinical testing
Color RCV000219745 SCV000908969 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000507009 SCV000920126 uncertain significance not specified 2017-10-31 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.53A>G (p.Gln18Arg) variant involves the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 7/242658 control chromosomes, predominantly observed in the South Asian subpopulation at a frequency of 0.000227 (7/30774). This frequency is about 2 times higher than the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125), which might suggest that this is likely a benign polymorphism found primarily in the populations of South Asian origin. 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. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. 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 RCV000409529 SCV001203913 uncertain significance Breast-ovarian cancer, familial 4 2019-11-14 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 18 of the RAD51D protein (p.Gln18Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs546225564, ExAC 0.02%). This variant has not been reported in the literature in individuals with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 232535). 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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