ClinVar Miner

Submissions for variant NM_032856.5(WDR73):c.766dup (p.Arg256fs)

dbSNP: rs727502864
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000150039 SCV001150307 pathogenic Galloway-Mowat syndrome 1 2019-12-30 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV000150039 SCV001164382 likely pathogenic Galloway-Mowat syndrome 1 2018-12-03 criteria provided, single submitter research The homozygous p.Arg256ProfsTer18 variant in WDR73 was identified by our study in one individual with Galloway-Mowat syndrome. This variant was seen in 0.006677% (1/14976) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs727502864). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The homozygous p.Arg256ProfsTer18 variant in WDR73 has been reported in one Turkish individual with Galloway-Mowat syndrome. This individual's unaffected parents and siblings were heterozygous for the variant or did not have the variant (PMID: 25466283). This nonsense variant leads to a premature termination codon at position 274, which is predicted to lead to a truncated or absent protein. A knock-out zebrafish model for the WDR73 gene has a phenotype that matches Galloway-Mowat syndrome and at least two loss of function variants across multiple exons have been reported in association with Galloway-Mowat syndrome in ClinVar (PMID: 25466283). Loss of function of the WDR73 gene is a moderately established disease mechanism in autosomal recessive Galloway-Mowat syndrome. This variant has also been reported pathogenic by OMIM in ClinVar (Variation ID: 162611). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015).
CeGaT Center for Human Genetics Tuebingen RCV002274932 SCV002563270 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
OMIM RCV000150039 SCV000196897 pathogenic Galloway-Mowat syndrome 1 2014-12-04 no assertion criteria provided literature only

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