4-83284576-C-A

Position:

• chr4-83284576-C-A

Variant summary

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

The NM_001358921.2(COQ2):​c.189G>T​(p.Val63Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,553,630 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (11 hom., cov: 34)
  • Exomes 𝑓: 0.00066 (6 hom.)
• Consequence: COQ2 NM_001358921.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -4.63

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=-0.61).
• BP6: Variant 4-83284576-C-A is Benign according to our data. Variant chr4-83284576-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 136980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.63 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00652 (992/152178) while in subpopulation AFR AF= 0.0224 (929/41552). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.189G>T	p.Val63Val	synonymous_variant	1/7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.339G>T	p.Val113Val	synonymous_variant	1/7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.189G>T	p.Val63Val	synonymous_variant	1/7		NM_001358921.2	ENSP00000495761.2
COQ2	ENST00000311469.9	c.339G>T	p.Val113Val	synonymous_variant	1/7	1		ENSP00000310873.4
COQ2	ENST00000311461.7	c.189G>T	p.Val63Val	synonymous_variant	1/7	5		ENSP00000311835.7
COQ2	ENST00000503391.5	n.189G>T		non_coding_transcript_exon_variant	1/7	2		ENSP00000426242.1

Frequencies

GnomAD3 genomes AF: 0.00652 AC: 992 AN: 152066 Hom.: 11 Cov.: 34

Gnomad AFR AF: 0.0224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00109 AC: 159 AN: 145330 Hom.: 2 AF XY: 0.000813 AC XY: 65 AN XY: 79968

Gnomad AFR exome AF: 0.0231

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000442

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000218

Gnomad OTH exome AF: 0.00100

GnomAD4 exome AF: 0.000664 AC: 930 AN: 1401452 Hom.: 6 Cov.: 84 AF XY: 0.000603 AC XY: 418 AN XY: 692790

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000377

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00131

GnomAD4 genome AF: 0.00652 AC: 992 AN: 152178 Hom.: 11 Cov.: 34 AF XY: 0.00626 AC XY: 466 AN XY: 74404

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.000472 Hom.: 0

Bravo AF: 0.00766

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Focal segmental glomerulosclerosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.13
DANN	Benign	0.65

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: rs368507578; hg19: chr4-84205729;