rs6535454

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001358921.2(COQ2):c.744T>C(p.Asp248Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,598,806 control chromosomes in the GnomAD database, including 415,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42874 hom., cov: 32)

Exomes 𝑓: 0.72 ( 372150 hom. )

Consequence

COQ2
NM_001358921.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 4-83269878-A-G is Benign according to our data. Variant chr4-83269878-A-G is described in ClinVar as [Benign]. Clinvar id is 128829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83269878-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2 link	c.744T>C	p.Asp248Asp	synonymous_variant	Exon 5 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9 link	c.894T>C	p.Asp298Asp	synonymous_variant	Exon 5 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.744T>C	p.Asp248Asp	synonymous_variant	Exon 5 of 7		NM_001358921.2	ENSP00000495761.2		Q96H96-1

Frequencies

GnomAD3 genomes

AF:

0.749

AC:

113854

AN:

152024

Hom.:

42844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.772

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.852

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.738

GnomAD3 exomes

AF:

0.735

AC:

177117

AN:

240834

Hom.:

65446

AF XY:

0.735

AC XY:

96265

AN XY:

131044

show subpopulations

Gnomad AFR exome

AF:

0.817

Gnomad AMR exome

AF:

0.700

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.794

Gnomad NFE exome

AF:

0.710

Gnomad OTH exome

AF:

0.719

GnomAD4 exome

AF:

0.716

AC:

1035979

AN:

1446664

Hom.:

372150

Cov.:

AF XY:

0.718

AC XY:

516508

AN XY:

719836

show subpopulations

Gnomad4 AFR exome

AF:

0.814

Gnomad4 AMR exome

AF:

0.697

Gnomad4 ASJ exome

AF:

0.679

Gnomad4 EAS exome

AF:

0.840

Gnomad4 SAS exome

AF:

0.746

Gnomad4 FIN exome

AF:

0.793

Gnomad4 NFE exome

AF:

0.704

Gnomad4 OTH exome

AF:

0.724

GnomAD4 genome

AF:

0.749

AC:

113936

AN:

152142

Hom.:

42874

Cov.:

AF XY:

0.754

AC XY:

56071

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.804

Gnomad4 AMR

AF:

0.717

Gnomad4 ASJ

AF:

0.684

Gnomad4 EAS

AF:

0.852

Gnomad4 SAS

AF:

0.741

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.709

Gnomad4 OTH

AF:

0.738

Alfa

AF:

0.718

Hom.:

24335

Bravo

AF:

0.744

Asia WGS

AF:

0.809

AC:

2817

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

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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. -

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 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 88. Only high quality variants are reported. -

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 11, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Coenzyme Q10 deficiency, primary, 1

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: 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

-0.53

CADD

Benign

7.0

DANN

Benign

0.36

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