Genetic Variant COQ2:c.763-942G>A (chr4-83268716-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001358921.2(COQ2):c.763-942G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,068 control chromosomes in the GnomAD database, including 25,439 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 25439 hom., cov: 32)

Consequence

COQ2
NM_001358921.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Publications

23 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.763-942G>A		intron_variant	Intron 5 of 6	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.913-942G>A		intron_variant	Intron 5 of 6		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2 link	c.763-942G>A		intron_variant	Intron 5 of 6		NM_001358921.2	ENSP00000495761.2		Q96H96-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85329

AN:

151950

Hom.:

25434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.601

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.728

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.566

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.561

AC:

85344

AN:

152068

Hom.:

25439

Cov.:

AF XY:

0.571

AC XY:

42442

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.354

AC:

14666

AN:

41452

American (AMR)

AF:

0.601

AC:

9173

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2050

AN:

3472

East Asian (EAS)

AF:

0.851

AC:

4408

AN:

5182

South Asian (SAS)

AF:

0.687

AC:

3317

AN:

4826

European-Finnish (FIN)

AF:

0.728

AC:

7684

AN:

10560

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.620

AC:

42134

AN:

67986

Other (OTH)

AF:

0.567

AC:

1197

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1801

3602

5402

7203

9004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.596

Hom.:

55081

Bravo

AF:

0.542

Asia WGS

AF:

0.756

AC:

2628

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.84

(source)

DANN

Benign

0.87

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over