rs1129617

Positions:

• chr4-83267697-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001358921.2(COQ2):​c.840C>T​(p.Ser280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,554,922 control chromosomes in the GnomAD database, including 57,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4329 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53542 hom.)
• Consequence: COQ2 NM_001358921.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.249

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=-0.79).
• BP6: Variant 4-83267697-G-A is Benign according to our data. Variant chr4-83267697-G-A is described in ClinVar as [Benign]. Clinvar id is 128830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83267697-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ2	NM_001358921.2	c.840C>T	p.Ser280=	synonymous_variant	6/7	ENST00000647002.2
COQ2	NM_015697.9	c.990C>T	p.Ser330=	synonymous_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ2	ENST00000647002.2	c.840C>T	p.Ser280=	synonymous_variant	6/7		NM_001358921.2	P2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34770 AN: 151906 Hom.: 4322 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.250

GnomAD3 exomes AF: 0.258 AC: 42199 AN: 163364 Hom.: 5771 AF XY: 0.262 AC XY: 22506 AN XY: 85990

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.135

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.273 AC: 383173 AN: 1402898 Hom.: 53542 Cov.: 33 AF XY: 0.273 AC XY: 189276 AN XY: 692402

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.322

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.229 AC: 34809 AN: 152024 Hom.: 4329 Cov.: 32 AF XY: 0.226 AC XY: 16780 AN XY: 74300

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.249

Alfa AF: 0.261 Hom.: 2375

Bravo AF: 0.230

Asia WGS AF: 0.200 AC: 692 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 01, 2011	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	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 48. Only high quality variants are reported. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Coenzyme Q10 deficiency, primary, 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 11, 2016	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.80

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: rs1129617; hg19: chr4-84188850; COSMIC: COSV61021267;