Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Molecular Genetics |
RCV001807789 | SCV002056140 | pathogenic | Neurodevelopmental disorder | 2021-12-15 | criteria provided, single submitter | research | |
| Victorian Clinical Genetics Services, |
RCV002274216 | SCV005086098 | pathogenic | Neurodevelopmental disorder with speech delay and variable ocular anomalies | 2023-12-21 | 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 neurodevelopmental disorder with speech delay and variable ocular anomalies (MIM#619989). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0204 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with at least 1/3 of the protein sequence affected. (SP) 0252 - This variant is homozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is expected to disrupt the THUMP domain (DECIPHER). (I) 0704 - Another premature termination variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Gln236*) has been reported as homozygous in three individuals with syndromic neurodevelopmental disorder in two families (PMID: 35196516). It has also been reported as a VUS by a clinical testing laboratory, however no further information was provided (ClinVar). In addition, p.(Leu258del) has been reported in three affected siblings with syndromic neurodevelopmental disorder (PMID: 35196516). (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) 1209 - This variant has been shown to be both maternally and paternally inherited (biallelic) (by research trio analysis, PMID: 35196516). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| OMIM | RCV002274216 | SCV002559871 | pathogenic | Neurodevelopmental disorder with speech delay and variable ocular anomalies | 2022-08-10 | no assertion criteria provided | literature only |