chr4-83268716-C-T

Position:

• chr4-83268716-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358921.2(COQ2):​c.763-942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,068 control chromosomes in the GnomAD database, including 25,439 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25439 hom., cov: 32)
• Consequence: COQ2 NM_001358921.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

Genes affected

COQ2 (HGNC:25223): (coenzyme Q2, polyprenyltransferase) This gene encodes an enzyme that functions in the final steps in the biosynthesis of CoQ (ubiquinone), a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This enzyme, which is part of the coenzyme Q10 pathway, catalyzes the prenylation of parahydroxybenzoate with an all-trans polyprenyl group. Mutations in this gene cause coenzyme Q10 deficiency, a mitochondrial encephalomyopathy, and also COQ2 nephropathy, an inherited form of mitochondriopathy with primary renal involvement. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.763-942G>A		intron_variant		ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.913-942G>A		intron_variant			NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.763-942G>A		intron_variant			NM_001358921.2	ENSP00000495761.2

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85329 AN: 151950 Hom.: 25434 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 85344 AN: 152068 Hom.: 25439 Cov.: 32 AF XY: 0.571 AC XY: 42442 AN XY: 74330

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.851

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.567

Alfa AF: 0.602 Hom.: 40632

Bravo AF: 0.542

Asia WGS AF: 0.756 AC: 2628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.84
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4693596; hg19: chr4-84189869;