Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV002810029 | SCV003761267 | likely pathogenic | Autosomal recessive ataxia due to ubiquinone deficiency | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Met613ThrfsTer112 variant in COQ8A was identified by our study, in the compound heterozygous state along with a variant of uncertain significance (dbSNP ID: rs760655614), in two siblings with primary coenzyme Q10 deficiency (Broad Institute Rare Genomes Project). The p.Met613ThrfsTer112 variant in COQ8A has not been previously reported in individuals with primary coenzyme Q10 deficiency 4. This variant was absent in large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 613 and leads to a premature termination codon 112 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the COQ8A gene is an established disease mechanism in autosomal recessive primary coenzyme Q10 deficiency 4. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive primary coenzyme Q10 deficiency. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PP1 (Richards 2015). |