Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001650842 | SCV001871146 | pathogenic | not provided | 2024-02-02 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate impaired autophagic clearance of protein aggregates and maintenance of cell viability (PMID: 33730050); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28969387, 22686558, 16371500, 33996189, 33724704, 34338917, 21885617, 33730050) |
| Fulgent Genetics, |
RCV002490408 | SCV002797677 | likely pathogenic | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2; Hydrocephalus, congenital, 3, with brain anomalies | 2022-03-29 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000024315 | SCV004020809 | pathogenic | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 | 2023-06-13 | criteria provided, single submitter | clinical testing | Variant summary: WDR81 c.2567C>T (p.Pro856Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.3e-05 in 154980 control chromosomes (gnomAD). c.2567C>T has been reported in the literature in the homozygous state in six siblings affected with Cerebellar Ataxia, Intellectual Disability, And Dysequilibrium Syndrome 2 (CAMRQ2) from a large consanguineous Turkish family (Gulsuner_2011). The variant was found to segregate with the disease phenotype in this kindred, where over 100 family members spanning 5 generations were sequenced. These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 21885617). Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic (n=1)/likely pathogenic (n=2). Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000024315 | SCV000045606 | pathogenic | Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2 | 2011-12-01 | no assertion criteria provided | literature only | |
| New York Genome Center | RCV001255004 | SCV001431093 | likely pathogenic | Intellectual disability | 2020-03-09 | no assertion criteria provided | clinical testing |