rs368507578

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001358921.2(COQ2):c.189G>T(p.Val63Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,553,630 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 34)

Exomes 𝑓: 0.00066 ( 6 hom. )

Consequence

COQ2
NM_001358921.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.63

Publications

2 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=-0.61).

BP6

Variant 4-83284576-C-A is Benign according to our data. Variant chr4-83284576-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 136980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00652 (992/152178) while in subpopulation AFR AF = 0.0224 (929/41552). AF 95% confidence interval is 0.0212. There are 11 homozygotes in GnomAd4. There are 466 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.189G>T	p.Val63Val	synonymous_variant	Exon 1 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.339G>T	p.Val113Val	synonymous_variant	Exon 1 of 7		NP_056512.5	Q96H96-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COQ2	ENST00000647002.2 link	c.189G>T	p.Val63Val	synonymous_variant	Exon 1 of 7		NM_001358921.2	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311469.9 link	c.339G>T	p.Val113Val	synonymous_variant	Exon 1 of 7	1		ENSP00000310873.4	Q96H96-4
COQ2	ENST00000311461.7 link	c.189G>T	p.Val63Val	synonymous_variant	Exon 1 of 7	5		ENSP00000311835.7	Q96H96-3E2QRG7
COQ2	ENST00000503391.5 link	n.189G>T		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000426242.1	E7EPM7

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00109

AC:

159

AN:

145330

AF XY:

0.000813

show subpopulations

Gnomad AFR exome

AF:

0.0231

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000218

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000664

AC:

930

AN:

1401452

Hom.:

Cov.:

AF XY:

0.000603

AC XY:

418

AN XY:

692790

show subpopulations

African (AFR)

AF:

0.0221

AC:

668

AN:

30160

American (AMR)

AF:

0.00147

AC:

AN:

36710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24870

East Asian (EAS)

AF:

0.00

AC:

AN:

35138

South Asian (SAS)

AF:

0.0000377

AC:

AN:

79536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48210

Middle Eastern (MID)

AF:

0.00182

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.000110

AC:

119

AN:

1083278

Other (OTH)

AF:

0.00131

AC:

AN:

58044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

114

172

229

286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00652

AC:

992

AN:

152178

Hom.:

Cov.:

AF XY:

0.00626

AC XY:

466

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0224

AC:

929

AN:

41552

American (AMR)

AF:

0.00262

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67966

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000472

Hom.:

Bravo

AF:

0.00766

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 28, 2013

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:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Focal segmental glomerulosclerosis

Benign:1

Jul 13, 2020

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.13

(source)

DANN

Benign

0.65

PhyloP100

-4.6

PromoterAI

-0.11

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(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