Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004788447 | SCV005397966 | likely pathogenic | Dystonia 27 | 2023-12-21 | 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: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene, and are associated with Bethlem myopathy 1 (MIM#158810), dystonia 27 (MIM#616411) and Ullrich congenital muscular dystrophy 1 (MIM#254090). (I) 0108 - This gene is associated with both recessive and dominant disease (OMIM). (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0311 - Multiple alternative nucleotide changes at the same canonical splice site are present in gnomAD (highest allele count v3: 6 heterozygotes, 0 homozygotes). (I) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0704 - Another canonical splice variant comparable to the one identified in this case has limited previous evidence for pathogenicity. c.8966-1G>C has been classified as pathogenic by multiple clinical laboratories in ClinVar, and has been reported in individuals with autosomal recessive dystonia (Mastermind). (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) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |