Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004789845 | SCV005400592 | likely pathogenic | Short-rib thoracic dysplasia 21 without polydactyly | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with orofaciodigital syndrome XV (MIM#617127), Joubert syndrome 38 (MIM#619476) and short-rib thoracic dysplasia 21 without polydactyly (MIM#619479). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0205 - 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 less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant truncates the annotated MNR family domain (DECIPHER). (I) 0704 - Another truncating variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Asp936fs*3) has been observed in two compound heterozygous brothers with Joubert syndrome. Patient fibroblasts showed a deficit in primary ciliation and improper Shh and Wnt signaling (PMID: 34523780). (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) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |