Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001865313 | SCV002290573 | uncertain significance | not provided | 2022-05-25 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with clinical features of COQ8A-related conditions (PMID: 24164873). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 375333). This variant is also known as p.Gln360_Tyr361ins*. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 of the COQ8A gene. It does not directly change the encoded amino acid sequence of the COQ8A protein. It affects a nucleotide within the consensus splice site. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000416399 | SCV003923142 | likely pathogenic | Autosomal recessive ataxia due to ubiquinone deficiency | 2023-03-28 | criteria provided, single submitter | clinical testing | Variant summary: CABC1 (COQ8A) c.1081-1_1082dupGTA is located in a canonical splice-site. The frequency of this variant in the general population could not be determined (not present in gnomAD). c.1081-1_1082dupGTA, reported to create an in-frame stop codon (p.Gln360_Tyr361ins*), has been documented in the literature in individuals affected with Autosomal Recessive Ataxia Due To Ubiquinone Deficiency (Mignot_2013, Traschutz_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV000416399 | SCV000494105 | not provided | Autosomal recessive ataxia due to ubiquinone deficiency | no assertion provided | literature only |