Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
RCV000150039 | SCV001150307 | pathogenic | Galloway-Mowat syndrome 1 | 2019-12-30 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
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). |
Ce |
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 |