rs6818847

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001358921.2(COQ2):c.46G>T(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,506,450 control chromosomes in the GnomAD database, including 363,568 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31940 hom., cov: 33)

Exomes 𝑓: 0.70 ( 331628 hom. )

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -1.25

Variant links:

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]

COQ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.564486E-7).

BP6

Variant 4-83284719-C-A is Benign according to our data. Variant chr4-83284719-C-A is described in ClinVar as [Benign]. Clinvar id is 128828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83284719-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.46G>T	p.Val16Leu	missense_variant	Exon 1 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.196G>T	p.Val66Leu	missense_variant	Exon 1 of 7		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ2	ENST00000647002.2 link	c.46G>T	p.Val16Leu	missense_variant	Exon 1 of 7		NM_001358921.2	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311469.9 link	c.196G>T	p.Val66Leu	missense_variant	Exon 1 of 7	1		ENSP00000310873.4	Q96H96-4
COQ2	ENST00000311461.7 link	c.46G>T	p.Val16Leu	missense_variant	Exon 1 of 7	5		ENSP00000311835.7	Q96H96-3E2QRG7
COQ2	ENST00000503391.5 link	n.46G>T		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000426242.1	E7EPM7

Frequencies

GnomAD3 genomes

AF:

0.634

AC:

96252

AN:

151874

Hom.:

31938

Cov.:

show subpopulations

Gnomad AFR

AF:

0.424

Gnomad AMI

AF:

0.658

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.656

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.699

Gnomad OTH

AF:

0.651

GnomAD3 exomes

AF:

0.716

AC:

75123

AN:

104870

Hom.:

27189

AF XY:

0.719

AC XY:

42283

AN XY:

58772

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.688

Gnomad ASJ exome

AF:

0.659

Gnomad EAS exome

AF:

0.885

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.790

Gnomad NFE exome

AF:

0.707

Gnomad OTH exome

AF:

0.693

GnomAD4 exome

AF:

0.698

AC:

944870

AN:

1354464

Hom.:

331628

Cov.:

AF XY:

0.700

AC XY:

467584

AN XY:

667978

show subpopulations

Gnomad4 AFR exome

AF:

0.422

Gnomad4 AMR exome

AF:

0.674

Gnomad4 ASJ exome

AF:

0.650

Gnomad4 EAS exome

AF:

0.885

Gnomad4 SAS exome

AF:

0.733

Gnomad4 FIN exome

AF:

0.790

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.686

GnomAD4 genome

AF:

0.633

AC:

96270

AN:

151986

Hom.:

31940

Cov.:

AF XY:

0.642

AC XY:

47705

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.656

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.725

Gnomad4 FIN

AF:

0.804

Gnomad4 NFE

AF:

0.699

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.664

Hom.:

5971

Bravo

AF:

0.613

TwinsUK

AF:

0.711

AC:

2638

ALSPAC

AF:

0.688

AC:

2653

ESP6500AA

AF:

0.549

AC:

1570

ESP6500EA

AF:

0.746

AC:

4779

ExAC

AF:

0.614

AC:

44725

Asia WGS

AF:

0.774

AC:

2692

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 23, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2011

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 85. Only high quality variants are reported. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 11, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Coenzyme Q10 deficiency, primary, 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.33

DANN

Benign

0.60

DEOGEN2

Benign

0.077

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.34

T;.;T

MetaRNN

Benign

9.6e-7

T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.20

.;N;N

REVEL

Benign

0.068

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.53

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.11, 0.057

MutPred

0.38

Gain of disorder (P = 0.0309);.;Gain of disorder (P = 0.0309);

MPC

0.15

ClinPred

0.0016

GERP RS

-2.7

gMVP

0.087

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over