Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000416071 | SCV000339822 | uncertain significance | not provided | 2016-06-22 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000416071 | SCV000493294 | likely pathogenic | not provided | 2016-09-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002271485 | SCV002555694 | uncertain significance | not specified | 2022-06-06 | criteria provided, single submitter | clinical testing | Variant summary: WDR73 c.1132delC (p.Arg378AlafsX25) causes a frameshift which results in an extension of the protein in the last exon. The variant allele was found at a frequency of 0.00061 in 159916 control chromosomes (gnomAD). The variant was reported in the homozygous state in a consangiunous couples who had a deceased daughter, however other pathogenic variants were also reported (IGHMPB2, DYNC2H1) and mimimal phenotype data was provided (Sallevelt_2021). To our knowledge, no occurrence of c.1132delC in individuals affected with Galloway-Mowat Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic (n=1), and one laboratory classified the variant as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV000416071 | SCV003508027 | uncertain significance | not provided | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change results in a frameshift in the WDR73 gene (p.Arg378Alafs*25). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the WDR73 protein and extend the protein by 23 additional amino acid residues. This variant is present in population databases (rs775472894, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with WDR73-related conditions. ClinVar contains an entry for this variant (Variation ID: 286399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |