Variant rs121918230 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_001358921.2(COQ2):c.740A>G(p.Tyr247Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2O:1

Conservation

PhyloP100: 7.99

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.982

PP5

Variant 4-83269882-T-C is Pathogenic according to our data. Variant chr4-83269882-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1436.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-83269882-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2 linkuse as main transcript	c.740A>G	p.Tyr247Cys	missense_variant	5/7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 linkuse as main transcript	c.890A>G	p.Tyr297Cys	missense_variant	5/7		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2 linkuse as main transcript	c.740A>G	p.Tyr247Cys	missense_variant	5/7		NM_001358921.2	ENSP00000495761.2		Q96H96-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246202

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454514

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Coenzyme Q10 deficiency, primary, 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2010

- -

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2022

Published functional studies suggest the Y297C variant reduces CoQ production to a moderate level (Lpez-Martn; Desbats et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17855635, 33426503, 16116126, 17374725, 20495179, 17332886, 27493029, 31660881, 23816342, 29296619, 35483523, 16400613) -

Coenzyme Q10 deficiency

Other:1

not provided, no classification provided

literature only

GeneReviews

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.50

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

.;.;D

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;.;D

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Pathogenic

1.1

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-8.7

.;D;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

.;D;D

Sift4G

Pathogenic

0.0

.;D;D

Polyphen

0.99

.;.;D

Vest4

0.98, 0.99

MutPred

0.86

Gain of glycosylation at Y251 (P = 0.0239);.;Gain of glycosylation at Y251 (P = 0.0239);

MVP

0.99

MPC

0.73

ClinPred

1.0

GERP RS

6.2

gMVP

0.92

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over