4-83284885-C-T

Position:

• chr4-83284885-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015697.9(COQ2):​c.30G>A​(p.Arg10Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,523,936 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (41 hom.)
• Consequence: COQ2 NM_015697.9 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0150

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-83284885-C-T is Benign according to our data. Variant chr4-83284885-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.015 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00437 (666/152304) while in subpopulation NFE AF= 0.0081 (551/68020). AF 95% confidence interval is 0.00754. There are 5 homozygotes in gnomad4. There are 288 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_015697.9	c.30G>A	p.Arg10Arg	synonymous_variant	1/7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000311469.9	c.30G>A	p.Arg10Arg	synonymous_variant	1/7	1		ENSP00000310873.4

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152186 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00810

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00375 AC: 484 AN: 129154 Hom.: 6 AF XY: 0.00334 AC XY: 234 AN XY: 70164

Gnomad AFR exome AF: 0.000716

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000143

Gnomad FIN exome AF: 0.00202

Gnomad NFE exome AF: 0.00786

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00644 AC: 8835 AN: 1371632 Hom.: 41 Cov.: 33 AF XY: 0.00616 AC XY: 4169 AN XY: 676766

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.000913

Gnomad4 ASJ exome AF: 0.0000803

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000284

Gnomad4 FIN exome AF: 0.00173

Gnomad4 NFE exome AF: 0.00789

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152304 Hom.: 5 Cov.: 32 AF XY: 0.00387 AC XY: 288 AN XY: 74480

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00810

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00401

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	COQ2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Coenzyme Q10 deficiency, primary, 1;C3714927:Multiple system atrophy 1, susceptibility to Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.78

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: rs183012002; hg19: chr4-84206038;