ClinVar Miner

Submissions for variant NM_020779.4(WDR35):c.1930C>G (p.Pro644Ala)

gnomAD frequency: 0.00001  dbSNP: rs758919526
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434466 SCV000535703 uncertain significance not provided 2017-01-23 criteria provided, single submitter clinical testing The P655A variant in the WDR35 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P655A variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P655A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P655A as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV002480326 SCV002787531 uncertain significance Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly 2024-05-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002480326 SCV003246910 uncertain significance Cranioectodermal dysplasia 2; Short-rib thoracic dysplasia 7 with or without polydactyly 2022-05-04 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 392433). This variant has not been reported in the literature in individuals affected with WDR35-related conditions. This variant is present in population databases (rs758919526, gnomAD 0.005%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 655 of the WDR35 protein (p.Pro655Ala).

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