ClinVar Miner

Submissions for variant NM_001242897.2(DEPDC5):c.5G>A (p.Arg2Lys) (rs756142773)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459734 SCV000546536 uncertain significance Familial focal epilepsy with variable foci 2019-04-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 2 of the DEPDC5 protein (p.Arg2Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs756142773, ExAC 0.02%). This variant has not been reported in the literature in individuals with DEPDC5-related disease. ClinVar contains an entry for this variant (Variation ID: 407350). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Integrated Genetics/Laboratory Corporation of America RCV001193557 SCV001362461 uncertain significance not specified 2019-03-22 criteria provided, single submitter clinical testing Variant summary: DEPDC5 c.5G>A (p.Arg2Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 277212 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in DEPDC5 causing Epilepsy, familial focal, with variable foci 1 (3.6e-05 vs ND), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.5G>A in individuals affected with Epilepsy, familial focal, with variable foci 1 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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