4-83264267-CA-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_001358921.2(COQ2):βc.1047delTβ(p.Asn351IlefsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Consequence
NM_001358921.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246558Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133836
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1458780Hom.: 0 Cov.: 30 AF XY: 0.0000317 AC XY: 23AN XY: 725626
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74242
ClinVar
Submissions by phenotype
Coenzyme Q10 deficiency, primary, 1;C3714927:Multiple system atrophy 1, susceptibility to Pathogenic:1
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Coenzyme Q10 deficiency, primary, 1 Pathogenic:1
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Asn401Ilefs*15) in the COQ2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acid(s) of the COQ2 protein. This variant is present in population databases (rs750710187, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with clinical features of coenzyme Q10 deficiency (PMID: 17332895). This variant is also known as c.1198delT (p.N401fsX415) and/or c.1047delT (p.Asn351Ilefs*14). ClinVar contains an entry for this variant (Variation ID: 375340). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects COQ2 function (PMID: 17332895, 27493029). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Coenzyme Q10 deficiency Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at