rs144913206

Positions:

chr4-83273614-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001358921.2(COQ2):c.424A>G(p.Thr142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,613,186 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010062784).

BP6

Variant 4-83273614-T-C is Benign according to our data. Variant chr4-83273614-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 136972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83273614-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00515 (785/152280) while in subpopulation AFR AF= 0.0179 (745/41540). AF 95% confidence interval is 0.0169. There are 2 homozygotes in gnomad4. There are 371 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ2	NM_001358921.2 linkuse as main transcript	c.424A>G	p.Thr142Ala	missense_variant	3/7	ENST00000647002.2
COQ2	NM_015697.9 linkuse as main transcript	c.574A>G	p.Thr192Ala	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ2	ENST00000647002.2 linkuse as main transcript	c.424A>G	p.Thr142Ala	missense_variant	3/7		NM_001358921.2	P2	Q96H96-1

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

783

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00131

AC:

325

AN:

248378

Hom.:

AF XY:

0.000838

AC XY:

113

AN XY:

134794

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000498

AC:

727

AN:

1460906

Hom.:

Cov.:

AF XY:

0.000429

AC XY:

312

AN XY:

726740

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00515

AC:

785

AN:

152280

Hom.:

Cov.:

AF XY:

0.00498

AC XY:

371

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0179

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000983

Hom.:

Bravo

AF:

0.00551

ESP6500AA

AF:

0.0147

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.00153

AC:

185

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	COQ2: BP4, BS1 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 11, 2016	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 23, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.21

DANN

Benign

0.76

DEOGEN2

Benign

0.35

.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.75

T;.;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.20

.;N;N

REVEL

Benign

0.22

Sift

Benign

0.64

.;T;T

Sift4G

Benign

0.71

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.10, 0.12

MVP

0.59

MPC

0.15

ClinPred

0.000037

GERP RS

0.18

gMVP

0.39

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