ClinVar

Description

DNA sequence analysis of the COQ2 gene demonstrated a one base pair duplication in exon 1, c.288dup. This duplication results in an amino acid frameshift and is predicted to create a premature stop codon 56 amino acids downstream of the change, p.Ala97Argfs*56. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated COQ2 protein with potentially abnormal function. However, there are multiple in-frame methionines in exon 1 of the COQ2 gene, and experimental studies have demonstrated that alternate methionines may be used as the initiation codon (PMID: 27493029). This sequence change has been described in the gnomAD database with a frequency of 0.37% in the Ashkenazi Jewish subpopulation (dbSNP rs759310292). This duplication has been previously described in the compound heterozygous state with a missense variant in a family of Ashkenazi Jewish ancestry with nephropathy and retinopathy, but without neurological involvement (PMID: 33187544). The functional significance of this sequence change is not known at present and its contribution to this individual's disease phenotype cannot definitively be determined.