rs778094136

Variant names:

• chr4-83284533-T-A
• rs778094136
• 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. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015697.9(COQ2):​c.382A>T​(p.Met128Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M128V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: COQ2 NM_015697.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015697.9. 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.232A>T	p.Met78Leu	missense	Exon 1 of 7	NP_001345850.1
	COQ2	NM_015697.9		c.382A>T	p.Met128Leu	missense	Exon 1 of 7	NP_056512.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	ENST00000647002.2	MANE Select	c.232A>T	p.Met78Leu	missense	Exon 1 of 7	ENSP00000495761.2
	COQ2	ENST00000311469.9	TSL:1	c.382A>T	p.Met128Leu	missense	Exon 1 of 7	ENSP00000310873.4
	COQ2	ENST00000311461.7	TSL:5	c.232A>T	p.Met78Leu	missense	Exon 1 of 7	ENSP00000311835.7

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

African (AFR) AF: 0.00 AC: 0 AN: 31560

American (AMR) AF: 0.00 AC: 0 AN: 40126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25328

East Asian (EAS) AF: 0.00 AC: 0 AN: 37102

South Asian (SAS) AF: 0.00 AC: 0 AN: 81546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49168

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095066

Other (OTH) AF: 0.00 AC: 0 AN: 58904

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.46	T
PhyloP100		4.6
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.38
Sift	Benign	0.057	T
Sift4G	Benign	0.19	T
Polyphen		0.13	B
Vest4		0.64
MutPred		0.56		Loss of helix (P = 0.0104)
MVP		0.66
MPC		0.17
ClinPred		0.60	D
GERP RS		2.2
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.67
Mutation Taster		=30/70	disease causing

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

Other links and lift over

dbSNP: rs778094136; hg19: chr4-84205686;