Genetic Variant COQ2:p.Arg10Arg (chr4-83284885-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015697.9(COQ2):c.30G>A(p.Arg10Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,523,936 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 41 hom. )

Consequence

COQ2
NM_015697.9 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0150

Publications

4 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: G2P, Labcorp Genetics (formerly Invitae)
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 4-83284885-C-T is Benign according to our data. Variant chr4-83284885-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.015 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00437 (666/152304) while in subpopulation NFE AF = 0.0081 (551/68020). AF 95% confidence interval is 0.00754. There are 5 homozygotes in GnomAd4. There are 288 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015697.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	NM_015697.9		c.30G>A	p.Arg10Arg	synonymous	Exon 1 of 7	NP_056512.5
	COQ2	NM_001358921.2	MANE Select	c.-121G>A		upstream_gene	N/A	NP_001345850.1	Q96H96-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ2	ENST00000311469.9	TSL:1	c.30G>A	p.Arg10Arg	synonymous	Exon 1 of 7	ENSP00000310873.4	Q96H96-4
COQ2	ENST00000647002.2	MANE Select	c.-121G>A		upstream_gene	N/A	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311461.7	TSL:5	c.-121G>A		upstream_gene	N/A	ENSP00000311835.7	Q96H96-3

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00810

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00375

AC:

484

AN:

129154

AF XY:

0.00334

show subpopulations

Gnomad AFR exome

AF:

0.000716

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00202

Gnomad NFE exome

AF:

0.00786

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00644

AC:

8835

AN:

1371632

Hom.:

Cov.:

AF XY:

0.00616

AC XY:

4169

AN XY:

676766

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

30334

American (AMR)

AF:

0.000913

AC:

AN:

33964

Ashkenazi Jewish (ASJ)

AF:

0.0000803

AC:

AN:

24914

East Asian (EAS)

AF:

0.00

AC:

AN:

34044

South Asian (SAS)

AF:

0.000284

AC:

AN:

77510

European-Finnish (FIN)

AF:

0.00173

AC:

AN:

34118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00789

AC:

8475

AN:

1073614

Other (OTH)

AF:

0.00365

AC:

210

AN:

57460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

444

889

1333

1778

2222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.00437

AC:

666

AN:

152304

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00142

AC:

AN:

41580

American (AMR)

AF:

0.000915

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00810

AC:

551

AN:

68020

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

101

135

169

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:

0.00177

Hom.:

Bravo

AF:

0.00401

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

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

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.4

(source)

DANN

Benign

0.78

PhyloP100

0.015

PromoterAI

-0.020

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over