ENST00000311469.9:c.64A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBS1BS2

The ENST00000311469.9(COQ2):c.64A>T(p.Arg22*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,546,968 control chromosomes in the GnomAD database, including 428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R22R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.018 ( 37 hom., cov: 32)

Exomes 𝑓: 0.022 ( 391 hom. )

Consequence

COQ2
ENST00000311469.9 stop_gained

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:10

Conservation

PhyloP100: -3.50

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

coenzyme Q10 deficiency, primary, 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
multiple system atrophy
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
Leigh syndrome with nephrotic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COQ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 36 pathogenic variants in the truncated region.

BP6

Variant 4-83284851-T-A is Benign according to our data. Variant chr4-83284851-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.018 (2736/152308) while in subpopulation NFE AF = 0.0257 (1748/68012). AF 95% confidence interval is 0.0247. There are 37 homozygotes in GnomAd4. There are 1312 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_015697.9 link	c.64A>T	p.Arg22*	stop_gained	Exon 1 of 7		NP_056512.5	Q96H96-4
COQ2	NM_001358921.2 link	c.-87A>T		upstream_gene_variant		ENST00000647002.2	NP_001345850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ2	ENST00000311469.9 link	c.64A>T	p.Arg22*	stop_gained	Exon 1 of 7	1		ENSP00000310873.4	Q96H96-4
COQ2	ENST00000647002.2 link	c.-87A>T		upstream_gene_variant			NM_001358921.2	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311461.7 link	c.-87A>T		upstream_gene_variant		5		ENSP00000311835.7	Q96H96-3E2QRG7
COQ2	ENST00000503391.5 link	n.-87A>T		upstream_gene_variant		2		ENSP00000426242.1	E7EPM7

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2737

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0317

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0180

AC:

2785

AN:

154366

AF XY:

0.0176

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0300

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0222

AC:

30922

AN:

1394660

Hom.:

391

Cov.:

AF XY:

0.0219

AC XY:

15087

AN XY:

689630

show subpopulations

African (AFR)

AF:

0.00451

AC:

142

AN:

31520

American (AMR)

AF:

0.0130

AC:

480

AN:

36856

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

713

AN:

25290

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35862

South Asian (SAS)

AF:

0.00341

AC:

270

AN:

79212

European-Finnish (FIN)

AF:

0.0289

AC:

1038

AN:

35976

Middle Eastern (MID)

AF:

0.0233

AC:

133

AN:

5714

European-Non Finnish (NFE)

AF:

0.0248

AC:

26939

AN:

1085784

Other (OTH)

AF:

0.0206

AC:

1206

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1737

3474

5211

6948

8685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

980

1960

2940

3920

4900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0180

AC:

2736

AN:

152308

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1312

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00503

AC:

209

AN:

41570

American (AMR)

AF:

0.0174

AC:

266

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00332

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0317

AC:

336

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0257

AC:

1748

AN:

68012

Other (OTH)

AF:

0.0204

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

145

289

434

578

723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0165

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.00418

AC:

ESP6500EA

AF:

0.0229

AC:

182

ExAC

AF:

0.0137

AC:

1530

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 198/11788=1.67% -

Feb 23, 2016

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 13, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 20, 2012

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. -

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 07, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

COQ2: BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Coenzyme Q10 deficiency, primary, 1

Uncertain:1

Jun 07, 2017

SingHealth Duke-NUS Institute of Precision Medicine

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:curation

- -

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

Benign:1

Oct 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis

Benign:1

Mar 14, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.44

(source)

DANN

Benign

0.96

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0035

PhyloP100

-3.5

Vest4

0.26

GERP RS

-4.1

PromoterAI

0.11

Neutral

(source)

Mutation Taster

=164/36

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over