Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788386 | SCV005400227 | uncertain significance | Infantile-onset generalized dyskinesia with orofacial involvement | 2023-07-16 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function is a known mechanism of diseaese and is associated with autosomal recessive dyskinesia, limb and orofacial, infantile-onset (MIM#616921; PMID: 27058446), while dominant negative has been suggested as the mechanism of autosomal dominant striatal degeneration (MIM#616922; PMID: 27058447). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated GAF-B domain (NCBI, PMID: 27058447). Variants in this domain are suggested to have a dominant negative effect and disrupt the positive regulation of the protein by cAMP (PMID: 27058447). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 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) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |