NM_001358921.2:c.1028T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001358921.2(COQ2):c.1028T>C(p.Val343Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,612,214 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. V343V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 25 hom. )

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.94

Publications

49 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008151174).

BP6

Variant 4-83264287-A-G is Benign according to our data. Variant chr4-83264287-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 214217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00188 (286/152270) while in subpopulation EAS AF = 0.0166 (86/5188). AF 95% confidence interval is 0.0137. There are 3 homozygotes in GnomAd4. There are 162 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.1028T>C	p.Val343Ala	missense_variant	Exon 7 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.1178T>C	p.Val393Ala	missense_variant	Exon 7 of 7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2 link	c.1028T>C	p.Val343Ala	missense_variant	Exon 7 of 7		NM_001358921.2	ENSP00000495761.2

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0163

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00415

AC:

1027

AN:

247460

AF XY:

0.00328

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00284

GnomAD4 exome

AF:

0.00112

AC:

1640

AN:

1459944

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

747

AN XY:

726142

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33386

American (AMR)

AF:

0.0183

AC:

815

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.0166

AC:

657

AN:

39576

South Asian (SAS)

AF:

0.000548

AC:

AN:

85702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1111292

Other (OTH)

AF:

0.00113

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

162

244

325

406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00188

AC:

286

AN:

152270

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41552

American (AMR)

AF:

0.0108

AC:

166

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0166

AC:

AN:

5188

South Asian (SAS)

AF:

0.00104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000960

Hom.:

Bravo

AF:

0.00289

ExAC

AF:

0.00363

AC:

439

Asia WGS

AF:

0.00376

AC:

AN:

3476

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 13, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 23, 2017

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.92

Eigen

Benign

0.16

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.89

D;.

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-0.35

PhyloP100

8.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

.;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.010

.;D

Vest4

0.36

MVP

0.79

MPC

0.20

ClinPred

0.072

GERP RS

6.2

gMVP

0.52

Mutation Taster

=64/36

polymorphism

(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