4-83271015-G-C

Variant names:

• chr4-83271015-G-C
• rs4693075
• NM_001358921.2:c.629-1022C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001358921.2(COQ2):​c.629-1022C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,976 control chromosomes in the GnomAD database, including 29,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (29234 hom., cov: 31)
• Consequence: COQ2 NM_001358921.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-83271015-G-C is Benign according to our data. Variant chr4-83271015-G-C is described in ClinVar as [Benign]. Clinvar id is 226000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.629-1022C>G		intron_variant	Intron 4 of 6	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.779-1022C>G		intron_variant	Intron 4 of 6		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.629-1022C>G		intron_variant	Intron 4 of 6		NM_001358921.2	ENSP00000495761.2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93643 AN: 151858 Hom.: 29223 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.616 AC: 93683 AN: 151976 Hom.: 29234 Cov.: 31 AF XY: 0.624 AC XY: 46379 AN XY: 74292

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.599

Alfa AF: 0.617 Hom.: 3477

Bravo AF: 0.606

Asia WGS AF: 0.764 AC: 2659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4693075; hg19: chr4-84192168;