4-83284571-T-G

Position:

chr4-83284571-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001358921.2(COQ2):c.194A>C(p.Asp65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000936 in 1,557,410 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0053 ( 11 hom., cov: 34)

Exomes 𝑓: 0.00046 ( 4 hom. )

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 0.163

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041458905).

BP6

Variant 4-83284571-T-G is Benign according to our data. Variant chr4-83284571-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218722.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=3}. Variant chr4-83284571-T-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00534 (811/151770) while in subpopulation AFR AF= 0.0186 (770/41392). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4. There are 387 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2 linkuse as main transcript	c.194A>C	p.Asp65Ala	missense_variant	1/7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 linkuse as main transcript	c.344A>C	p.Asp115Ala	missense_variant	1/7		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COQ2	ENST00000647002.2 linkuse as main transcript	c.194A>C	p.Asp65Ala	missense_variant	1/7		NM_001358921.2	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311469.9 linkuse as main transcript	c.344A>C	p.Asp115Ala	missense_variant	1/7	1		ENSP00000310873.4	Q96H96-4
COQ2	ENST00000311461.7 linkuse as main transcript	c.194A>C	p.Asp65Ala	missense_variant	1/7	5		ENSP00000311835.7	Q96H96-3E2QRG7
COQ2	ENST00000503391.5 linkuse as main transcript	n.194A>C		non_coding_transcript_exon_variant	1/7	2		ENSP00000426242.1	E7EPM7

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

807

AN:

151654

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000773

AC:

117

AN:

151298

Hom.:

AF XY:

0.000671

AC XY:

AN XY:

83454

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000433

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000341

Gnomad OTH exome

AF:

0.000245

GnomAD4 exome

AF:

0.000460

AC:

647

AN:

1405640

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

281

AN XY:

695252

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.000724

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000626

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000157

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00534

AC:

811

AN:

151770

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

387

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0186

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00620

ESP6500AA

AF:

0.00876

AC:

ESP6500EA

AF:

0.000150

AC:

ExAC

AF:

0.000719

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Jun 17, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 17, 2019	- -

Focal segmental glomerulosclerosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.3

DANN

Benign

0.53

DEOGEN2

Benign

0.096

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.54

T;.;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.6

.;N;N

REVEL

Benign

0.16

Sift

Benign

0.13

.;T;T

Sift4G

Benign

0.13

.;T;T

Polyphen

0.0

.;.;B

Vest4

0.064, 0.090

MVP

0.42

MPC

0.20

ClinPred

0.0054

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.38

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