rs397514727

Positions:

• chr4-83267659-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 15/19 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
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23018861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.878T>C	p.Val293Ala	missense_variant	6/7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.1028T>C	p.Val343Ala	missense_variant	6/7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.878T>C	p.Val293Ala	missense_variant	6/7		NM_001358921.2	ENSP00000495761.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423204 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704414

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Multiple system atrophy Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 03, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	9.4
DANN	Benign	0.49
DEOGEN2	Benign	0.35	.;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.54	T;.;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.64	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.5	.;N;N
REVEL	Benign	0.22
Sift	Benign	1.0	.;T;T
Sift4G	Benign	1.0	.;T;T
Polyphen		0.0	.;.;B
Vest4		0.20, 0.18
MutPred		0.71		Loss of glycosylation at S297 (P = 0.0243);.;Loss of glycosylation at S297 (P = 0.0243);
MVP		0.74
MPC		0.19
ClinPred		0.062	T
GERP RS		1.3
gMVP		0.42

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

Other links and lift over

dbSNP: rs397514727; hg19: chr4-84188812;