Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Molecular Pathology, |
RCV002272765 | SCV002556943 | likely pathogenic | Hydrocephalus, congenital, 3, with brain anomalies | 2021-06-23 | criteria provided, single submitter | clinical testing | The WDR81 c.3843C>A variant is a single nucleotide change in exon 3 of 10 which is predicted to result in a premature termination of the protein product at codon 1281. This is a predicted null variant for all biologically relevant transcripts and null variants in this gene are a known mechanism of disease (PVS1). The gene is constraint for loss-of-function variants and other nonsense/ stop gain variants have been reported downstream of this variant. This variant is absent from population databases (PM2). This variant has not been reported in dbSNP, ClinVar or HGMD. This variant is maternally inherited. |
| Victorian Clinical Genetics Services, |
RCV004594631 | SCV003921922 | pathogenic | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with WDR81-related neurodevelopmental disorder. (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0402 - Variant is located in a gene associated with a severe early-onset recessive condition that is intolerant to biallelic loss of function variants (gnomAD, OMIM). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. More than ten other variants predicted to result in a loss of function have previously been reported in individuals with WDR81-related neurodevelopmental disorders. (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |