4-83284851-T-A

Position:

chr4-83284851-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBS1BS2

The ENST00000311469.9(COQ2):c.64A>T(p.Arg22Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,546,968 control chromosomes in the GnomAD database, including 428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R22R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.018 ( 37 hom., cov: 32)

Exomes 𝑓: 0.022 ( 391 hom. )

Consequence

COQ2
ENST00000311469.9 stop_gained

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:8

Conservation

PhyloP100: -3.50

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 -8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 28 pathogenic variants in the truncated region.

BP6

Variant 4-83284851-T-A is Benign according to our data. Variant chr4-83284851-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 136978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83284851-T-A is described in Lovd as [Likely_benign]. Variant chr4-83284851-T-A is described in Lovd as [Benign]. Variant chr4-83284851-T-A is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.018 (2736/152308) while in subpopulation NFE AF= 0.0257 (1748/68012). AF 95% confidence interval is 0.0247. There are 37 homozygotes in gnomad4. There are 1312 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ2	NM_015697.9 linkuse as main transcript	c.64A>T	p.Arg22Ter	stop_gained	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ2	ENST00000311469.9 linkuse as main transcript	c.64A>T	p.Arg22Ter	stop_gained	1/7	1		A2	Q96H96-4

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2737

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00504

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0174

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0317

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0257

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0180

AC:

2785

AN:

154366

Hom.:

AF XY:

0.0176

AC XY:

1482

AN XY:

84120

show subpopulations

Gnomad AFR exome

AF:

0.00335

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.0300

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0199

GnomAD4 exome

AF:

0.0222

AC:

30922

AN:

1394660

Hom.:

391

Cov.:

AF XY:

0.0219

AC XY:

15087

AN XY:

689630

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.0130

Gnomad4 ASJ exome

AF:

0.0282

Gnomad4 EAS exome

AF:

0.0000279

Gnomad4 SAS exome

AF:

0.00341

Gnomad4 FIN exome

AF:

0.0289

Gnomad4 NFE exome

AF:

0.0248

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0180

AC:

2736

AN:

152308

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1312

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.0174

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0317

Gnomad4 NFE

AF:

0.0257

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0165

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.00418

AC:

ESP6500EA

AF:

0.0229

AC:

182

ExAC

AF:

0.0137

AC:

1530

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 23, 2016	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2012	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. -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 198/11788=1.67% -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 13, 2017	- -

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Mar 07, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Coenzyme Q10 deficiency, primary, 1

Uncertain:1

Uncertain significance, no assertion criteria provided

curation

SingHealth Duke-NUS Institute of Precision Medicine

Jun 07, 2017

- -

Coenzyme Q10 deficiency, primary, 1;C3714927:Multiple system atrophy 1, susceptibility to

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 02, 2021

- -

Focal segmental glomerulosclerosis

Benign:1

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

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.44

DANN

Benign

0.96

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0035

MutationTaster

Benign

1.0

A;N

Vest4

0.26

GERP RS

-4.1

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