4-83264296-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP3_ModerateBS1_Supporting
The NM_001358921.2(COQ2):āc.1019G>Cā(p.Gly340Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001358921.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247488Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134248
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460218Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 726276
GnomAD4 genome AF: 0.000164 AC: 25AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.000256 AC XY: 19AN XY: 74246
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 390 of the COQ2 protein (p.Gly390Ala). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with coenzyme Q10 deficiency (PMID: 28044327, 35483523). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2203549). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COQ2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects COQ2 function (PMID: 28044327). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at