ClinVar Miner

Submissions for variant NM_032856.5(WDR73):c.888del (p.Phe296fs)

dbSNP: rs869320712
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224128 SCV000281346 pathogenic not provided 2016-04-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000224128 SCV001585598 pathogenic not provided 2023-08-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe296Leufs*26) in the WDR73 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the WDR73 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with autosomal recessive Galloway-Mowat syndrome in this population (PMID: 26070982). It is commonly reported in individuals of Amish ancestry (PMID: 26070982). ClinVar contains an entry for this variant (Variation ID: 225244). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects WDR73 function (PMID: 26070982). This variant disrupts the C-terminus of the WDR73 protein. Other variant(s) that disrupt this region (p.Gln314*) have been observed in individuals with WDR73-related conditions (PMID: 26123727). This suggests that this may be a clinically significant region of the protein. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000224128 SCV001787156 pathogenic not provided 2022-12-16 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation, as the last 83 amino acids are replaced with 25 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28720660, 30008475, 31028937, 26070982, 24077912)
Revvity Omics, Revvity RCV000210866 SCV002020906 pathogenic Galloway-Mowat syndrome 1 2020-04-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004547506 SCV004115972 pathogenic WDR73-related disorder 2023-06-09 criteria provided, single submitter clinical testing The WDR73 c.888delT variant is predicted to result in a frameshift and premature protein termination (p.Phe296Leufs*26). This variant has been reported to be causative for Galloway-Mowat syndrome (Jinks et al. PubMed ID: 26070982; Thiffault et al. 2018. PubMed ID: 30008475). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in WDR73 are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000210866 SCV000267191 pathogenic Galloway-Mowat syndrome 1 2017-10-27 no assertion criteria provided literature only

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