Genetic Variant NM_001358921.2:c.878T>C (chr4-83267659-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001358921.2(COQ2):c.878T>C(p.Val293Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COQ2
NM_001358921.2 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 2.82

Publications

15 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: G2P, Labcorp Genetics (formerly Invitae)
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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23018861).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	NM_001358921.2	MANE Select	c.878T>C	p.Val293Ala	missense	Exon 6 of 7	NP_001345850.1	Q96H96-1
	COQ2	NM_015697.9		c.1028T>C	p.Val343Ala	missense	Exon 6 of 7	NP_056512.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COQ2	ENST00000647002.2	MANE Select	c.878T>C	p.Val293Ala	missense	Exon 6 of 7	ENSP00000495761.2	Q96H96-1
COQ2	ENST00000311469.9	TSL:1	c.1028T>C	p.Val343Ala	missense	Exon 6 of 7	ENSP00000310873.4	Q96H96-4
COQ2	ENST00000503915.5	TSL:1	n.569T>C		non_coding_transcript_exon	Exon 5 of 7	ENSP00000427146.1	H0YAI0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1423204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704414

African (AFR)

AF:

0.00

AC:

AN:

32370

American (AMR)

AF:

0.00

AC:

AN:

39062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25456

East Asian (EAS)

AF:

0.00

AC:

AN:

37258

South Asian (SAS)

AF:

0.00

AC:

AN:

80784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092698

Other (OTH)

AF:

0.00

AC:

AN:

59016

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Multiple system atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.4

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.35

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.54

M_CAP

Benign

0.063

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.64

PhyloP100

2.8

PrimateAI

Benign

0.36

PROVEAN

Benign

2.5

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.71

Loss of glycosylation at S297 (P = 0.0243)

MVP

0.74

MPC

0.19

ClinPred

0.062

GERP RS

1.3

gMVP

0.42

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over