ClinVar Miner

Submissions for variant NM_020779.4(WDR35):c.2164C>T (p.Arg722Cys)

gnomAD frequency: 0.00011  dbSNP: rs374073530
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002153 SCV001160008 uncertain significance not specified 2018-10-06 criteria provided, single submitter clinical testing The WDR35 c.2197C>T; p.Arg733Cys variant (rs374073530), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the African population with an allele frequency of 0.037% (9/24,034 alleles) in the Genome Aggregation Database. The arginine at codon 733 is highly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg733Cys variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001351708 SCV001546202 uncertain significance Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly 2021-08-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 733 of the WDR35 protein (p.Arg733Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs374073530, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with WDR35-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV002264992 SCV002546743 uncertain significance not provided 2022-06-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV001351708 SCV005654930 uncertain significance Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly 2024-05-16 criteria provided, single submitter clinical testing

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