ClinVar Miner

Submissions for variant NM_001242896.3(DEPDC5):c.2533C>T (p.Arg845Cys)

gnomAD frequency: 0.00001  dbSNP: rs780652126
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001893951 SCV002126254 uncertain significance Familial focal epilepsy with variable foci 2024-02-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 845 of the DEPDC5 protein (p.Arg845Cys). This variant is present in population databases (rs780652126, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1357298). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV003339766 SCV004047107 uncertain significance Epilepsy, familial focal, with variable foci 1 criteria provided, single submitter clinical testing The missense variant in c.2533C>T (p.Arg845Cys) in DEPDC5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg845Cys variant is reported with the allele frequency of 0.001072% in gnomAD and is novel (not in any individuals) in 1000 Genomes. The amino acid Arg at position 845 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Arg845Cys in DEPDC5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Clinical Genomics Laboratory, Washington University in St. Louis RCV003339766 SCV005688707 uncertain significance Epilepsy, familial focal, with variable foci 1 2023-10-28 criteria provided, single submitter clinical testing The DEPDC5 c.2533C>T (p.Arg845Cys) variant, to our knowledge, has not been reported in the medical literature. This variant is only observed on 2/248,326 alleles in the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors suggest that the variant does not impact DEPDC5 function. This variant has been reported in the ClinVar database as a variant of uncertain significance by one submitter. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

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