Genetic Variant COQ2:p.Arg22Gly (chr4-83284851-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000311469.9(COQ2):c.64A>G(p.Arg22Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R22K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COQ2
ENST00000311469.9 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04284668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_015697.9 link	c.64A>G	p.Arg22Gly	missense_variant	Exon 1 of 7		NP_056512.5	Q96H96-4
COQ2	NM_001358921.2 link	c.-87A>G		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>G	p.Arg22Gly	missense_variant	Exon 1 of 7	1		ENSP00000310873.4	Q96H96-4
COQ2	ENST00000647002.2 link	c.-87A>G		upstream_gene_variant			NM_001358921.2	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311461.7 link	c.-87A>G		upstream_gene_variant		5		ENSP00000311835.7	Q96H96-3E2QRG7
COQ2	ENST00000503391.5 link	n.-87A>G		upstream_gene_variant		2		ENSP00000426242.1	E7EPM7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394702

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689652

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31520

American (AMR)

AF:

0.00

AC:

AN:

36856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25290

East Asian (EAS)

AF:

0.00

AC:

AN:

35862

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35978

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085824

Other (OTH)

AF:

0.00

AC:

AN:

58446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.56

(source)

DANN

Benign

0.95

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0054

M_CAP

Benign

0.025

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.93

PhyloP100

-3.5

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.24

REVEL

Benign

0.096

Sift

Benign

1.0

Sift4G

Pathogenic

0.0

Vest4

0.11

MutPred

0.28

Loss of MoRF binding (P = 0.007);

MVP

0.23

MPC

0.33

ClinPred

0.066

GERP RS

-4.1

PromoterAI

0.14

Neutral

(source)

gMVP

0.23

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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