ClinVar Miner

Submissions for variant NM_025132.4(WDR19):c.3533G>A (p.Arg1178Gln) (rs79436363)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433622 SCV000516765 likely pathogenic not provided 2017-05-30 criteria provided, single submitter clinical testing The R1178Q variant in the WDR19 gene has been reported previously in the homozygous andcompound heterozygous states in patients with WDR19-related disorders (Halbritter et al., 2013; Leeet al., 2015; Zhang et al., 2016). Immunohistochemical studies performed on renal biopsies of twopatients compound heterozygous for the R1178Q variant showed diffuse cytoplasmic localization ofthe protein compared to controls (Lee et al., 2015). Furthermore, the R1178Q variant is not observedat a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium etal., 2015; Exome Variant Server). The R1178Q variant is a semi-conservative amino acid substitution,which may impact secondary protein structure as these residues differ in some properties. Thissubstitution occurs at a position that is highly conserved across species. In silico analysis predicts thisvariant is probably damaging to the protein structure/function. Based on currently available evidence, R1178Q is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.
Invitae RCV000653250 SCV000775126 pathogenic Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 2017-09-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1178 of the WDR19 protein (p.Arg1178Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs79436363, ExAC 0.06%). This variant has been reported in the literature in multiple individuals affected with nephronophthisis (PMID: 23559409, 25726036), cranioectodermal dysplasia (PMID: 28621010), and retinitis pigmentosa (PMID: 27596865). It has also been found to segregate with nephronophthisis in a single family (PMID: 25726036). ClinVar contains an entry for this variant (Variation ID: 127158). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Rare Disease Group, Clinical Genetics,Karolinska Institutet RCV000754960 SCV000788386 uncertain significance Cranioectodermal dysplasia 2018-05-01 criteria provided, single submitter research
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000433622 SCV000860737 pathogenic not provided 2018-04-24 criteria provided, single submitter clinical testing
Department of Genetics,Sultan Qaboos University Hospital, Oman RCV000115014 SCV000891658 uncertain significance Senior-Loken syndrome 8 2017-12-30 criteria provided, single submitter curation
Baylor Genetics RCV000850617 SCV000992850 pathogenic Nephronophthisis 13; Senior-Loken syndrome 8 2017-12-31 criteria provided, single submitter clinical testing
OMIM RCV000115014 SCV000148923 pathogenic Senior-Loken syndrome 8 2013-08-01 no assertion criteria provided literature only

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