Submissions for variant NM_001358921.2(COQ2):c.138dup (p.Ala47fs)

dbSNP: rs759310292

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000930683	SCV001076338	likely benign	not provided	2024-12-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001535863	SCV001752478	likely pathogenic	Coenzyme Q10 deficiency, primary, 1; Multiple system atrophy	2021-06-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000930683	SCV004014609	likely pathogenic	not provided	2023-07-17	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30487145, 35483523, 33187544)
Mayo Clinic Laboratories, Mayo Clinic	RCV000930683	SCV005413644	likely pathogenic	not provided	2024-03-20	criteria provided, single submitter	clinical testing	PM2, PVS1
Fulgent Genetics, Fulgent Genetics	RCV005047028	SCV005669866	likely pathogenic	Coenzyme Q10 deficiency, primary, 1; Multiple system atrophy 1, susceptibility to	2023-12-27	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003151146	SCV003839370	uncertain significance	not specified	2022-03-07	no assertion criteria provided	clinical testing	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.