Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002231195 | SCV007096820 | pathogenic | Short-rib thoracic dysplasia 11 with or without polydactyly | 2025-07-24 | criteria provided, single submitter | clinical testing | This variant is classified as Pathogenic. Evidence in support of pathogenic classification: Variant is present in gnomAD <0.01 for a recessive condition (v4: 23 heterozygote(s), 0 homozygote(s)); This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in homozygous and compound heterozygous individuals affected with short-rib thoracic dysplasia 11 with or without polydactyly (PMIDs: 29241935, 29068549, 36653407). In addition, it has been classified as pathogenic and likely pathogenic by clinical laboratories (ClinVar); Missense variant predicted to be damaging by in silico tool(s) or highly conserved with a major amino acid change. Additional information: Variant is predicted to result in a missense amino acid change from Arg to Trp; This variant is heterozygous; This gene is associated with autosomal recessive disease; Alternative amino acid change(s) at the same position are present in gnomAD (highest allele count: v4: 8 heterozygote(s), 0 homozygote(s); No comparable missense variants have previous evidence for pathogenicity; Variant is not located in an established domain, motif, hotspot or informative constraint region; Loss of function is a known mechanism of disease in this gene and is associated with short-rib thoracic dysplasia 11 with or without polydactyly (MIM#615633). |
| Gene |
RCV003321641 | SCV006308207 | likely pathogenic | not provided | 2025-02-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging effect on protein stability, localization, and dynein-2 complex interaction (PMID: 36268591); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29068549, 36268591, 34406647, 36653407, 29241935) |
| Institute for Clinical Genetics, |
RCV003321641 | SCV004026493 | likely pathogenic | not provided | 2021-12-14 | criteria provided, single submitter | clinical testing | PP3, PM1, PM2_SUP, PP1_MOD |
| Labcorp Genetics |
RCV002231195 | SCV002508991 | pathogenic | Short-rib thoracic dysplasia 11 with or without polydactyly | 2025-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 182 of the WDR34 protein (p.Arg182Trp). This variant is present in population databases (rs555811074, gnomAD 0.006%). This missense change has been observed in individuals with short-rib thoracic dysplasia (PMID: 29068549, 29241935, 36653407; internal data). ClinVar contains an entry for this variant (Variation ID: 446625). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects WDR34 function (PMID: 36268591). For these reasons, this variant has been classified as Pathogenic. |
| University of Washington Center for Mendelian Genomics, |
RCV000515869 | SCV001479908 | likely pathogenic | Jeune thoracic dystrophy | no assertion criteria provided | research | ||
| Dan Cohn Lab, |
RCV000515869 | SCV000612031 | pathogenic | Jeune thoracic dystrophy | 2017-06-01 | no assertion criteria provided | research |