chr4-83267697-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001358921.2(COQ2):c.840C>T(p.Ser280Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,554,922 control chromosomes in the GnomAD database, including 57,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4329 hom., cov: 32)

Exomes 𝑓: 0.27 ( 53542 hom. )

Consequence

COQ2
NM_001358921.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.249

Publications

24 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-83267697-G-A is Benign according to our data. Variant chr4-83267697-G-A is described in ClinVar as Benign. ClinVar VariationId is 128830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.249 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.840C>T	p.Ser280Ser	synonymous_variant	Exon 6 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.990C>T	p.Ser330Ser	synonymous_variant	Exon 6 of 7		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2 link	c.840C>T	p.Ser280Ser	synonymous_variant	Exon 6 of 7		NM_001358921.2	ENSP00000495761.2		Q96H96-1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34770

AN:

151906

Hom.:

4322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.230

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.258

AC:

42199

AN:

163364

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.286

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.210

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.273

AC:

383173

AN:

1402898

Hom.:

53542

Cov.:

AF XY:

0.273

AC XY:

189276

AN XY:

692402

show subpopulations

African (AFR)

AF:

0.133

AC:

4214

AN:

31702

American (AMR)

AF:

0.290

AC:

10410

AN:

35958

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

8106

AN:

25198

East Asian (EAS)

AF:

0.138

AC:

4954

AN:

35914

South Asian (SAS)

AF:

0.282

AC:

22358

AN:

79320

European-Finnish (FIN)

AF:

0.211

AC:

10487

AN:

49714

Middle Eastern (MID)

AF:

0.302

AC:

1712

AN:

5664

European-Non Finnish (NFE)

AF:

0.282

AC:

305383

AN:

1081152

Other (OTH)

AF:

0.267

AC:

15549

AN:

58276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

13885

27770

41654

55539

69424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10328

20656

30984

41312

51640

<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

AF:

0.229

AC:

34809

AN:

152024

Hom.:

4329

Cov.:

AF XY:

0.226

AC XY:

16780

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.137

AC:

5660

AN:

41458

American (AMR)

AF:

0.271

AC:

4136

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1121

AN:

3470

East Asian (EAS)

AF:

0.134

AC:

692

AN:

5160

South Asian (SAS)

AF:

0.286

AC:

1377

AN:

4822

European-Finnish (FIN)

AF:

0.199

AC:

2099

AN:

10564

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.278

AC:

18911

AN:

67964

Other (OTH)

AF:

0.249

AC:

525

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1343

2686

4029

5372

6715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.257

Hom.:

3193

Bravo

AF:

0.230

Asia WGS

AF:

0.200

AC:

692

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 48. Only high quality variants are reported. -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2011

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 11, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Coenzyme Q10 deficiency, primary, 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.1

(source)

DANN

Benign

0.80

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over