ClinVar Miner

Submissions for variant NM_020247.5(COQ8A):c.1844dup (p.Ser616fs) (rs764847439)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195954 SCV000251075 pathogenic not provided 2019-01-17 criteria provided, single submitter clinical testing The c.1844dupG variant in the ADCK3 gene causes a frameshift starting with codon Serine 616, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 114 of the new reading frame, denoted p.Ser616LeufsX114. This mutation is predicted to cause loss of normal protein function by resulting in the replacement of the last 32 amino acids of the ADCK3 protein by 113 incorrect amino acids, which is predicted to affect the secondary structure and function of the ADCK3 protein. Although this variant has not been previously reported to our knowledge, it is expected to be a pathogenic variant.
Athena Diagnostics Inc RCV000195954 SCV000612251 pathogenic not provided 2017-02-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778224 SCV000914392 uncertain significance ADCK3-Related Disorders 2018-10-30 criteria provided, single submitter clinical testing The ADCK3 c.1844dupG (p.Ser616LeufsTer114) variant results in a frameshift, and is predicted to cause an elongation of the protein. This variant is located in the last exon of the gene and may escape nonsense-mediated decay. The p.Ser616LeufsTer114 variant has been reported in one study in which it was identified in a homozygous state in two affected siblings with an adolescence onset of cerebellar ataxia and severe myoclonus from a consanguineous Pakistani family (Liu et al. 2014). Patient fibroblasts from the proband showed significantly reduced levels of coenzyme Q10 (CoQ10) and reduced activity of mitochondrial complex I and complexes IIΓÇôIII compared to controls. Furthermore, the symptoms of the proband improved upon treatment with CoQ10. Control data are unavailable for this variant, which is reported at a frequency of 0.0003180 in the East Asian population of the Genome Aggregation Database. Based on the limited evidence and potential impact of frameshift variants, the ADCK3 p.Ser616LeufsTer114 variant is classified as a variant of unknown significance but suspicious for pathogenicity for an autosomal recessive form of spinocerebellar ataxia associated with primary coenzyme Q10 deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneReviews RCV000416393 SCV000494107 pathogenic Coenzyme Q10 deficiency, primary, 4 2016-06-07 no assertion criteria provided literature only

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