4-83264280-T-TA
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_001358921.2(COQ2):c.1034dupT(p.Leu345PhefsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000197 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001358921.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247412Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134334
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460194Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726358
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74314
ClinVar
Submissions by phenotype
not provided Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the COQ2 protein in which other variant(s) (p.Asn401Ilefs*15) have been determined to be pathogenic (PMID: 17332895, 27493029). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with COQ2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Leu395Phefs*24) in the COQ2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 27 amino acid(s) of the COQ2 protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at