rs778094136

Variant names:

• chr4-83284533-T-A
• NM_001358921.2:c.232A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-83284533-T-A
• chr4-83284533-T-C
• chr4-83284533-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001358921.2(COQ2):​c.232A>T​(p.Met78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000702 in 1,424,446 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: COQ2 NM_001358921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.232A>T	p.Met78Leu	missense_variant	Exon 1 of 7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.382A>T	p.Met128Leu	missense_variant	Exon 1 of 7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.232A>T	p.Met78Leu	missense_variant	Exon 1 of 7		NM_001358921.2	ENSP00000495761.2
COQ2	ENST00000311469.9	c.382A>T	p.Met128Leu	missense_variant	Exon 1 of 7	1		ENSP00000310873.4
COQ2	ENST00000311461.7	c.232A>T	p.Met78Leu	missense_variant	Exon 1 of 7	5		ENSP00000311835.7
COQ2	ENST00000503391.5	n.232A>T		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000426242.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424446 Hom.: 0 Cov.: 84 AF XY: 0.00 AC XY: 0 AN XY: 705924

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Benign	0.79
DEOGEN2	Benign	0.12	.;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.62	D
LIST_S2	Pathogenic	0.97	D;.;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.46	T
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	.;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.057	.;T;T
Sift4G	Benign	0.19	.;T;T
Polyphen		0.13	.;.;B
Vest4		0.64, 0.64
MutPred		0.56		Loss of helix (P = 0.0104);.;Loss of helix (P = 0.0104);
MVP		0.66
MPC		0.17
ClinPred		0.60	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-84205686;