rs1057519348

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001358921.2(COQ2):​c.395T>G​(p.Met132Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

COQ2
NM_001358921.2 missense

Scores

14
3
1

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 8.87
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COQ2NM_001358921.2 linkuse as main transcriptc.395T>G p.Met132Arg missense_variant 2/7 ENST00000647002.2
COQ2NM_015697.9 linkuse as main transcriptc.545T>G p.Met182Arg missense_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COQ2ENST00000647002.2 linkuse as main transcriptc.395T>G p.Met132Arg missense_variant 2/7 NM_001358921.2 P2Q96H96-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

Coenzyme Q10 deficiency Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.88
.;.;D
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;.;D
M_CAP
Pathogenic
0.29
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Pathogenic
1.0
D
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.5
.;D;D
REVEL
Pathogenic
0.96
Sift
Uncertain
0.0010
.;D;D
Sift4G
Pathogenic
0.0010
.;D;D
Polyphen
0.94
.;.;P
Vest4
0.94, 0.95
MutPred
0.85
Gain of glycosylation at Y137 (P = 0.046);.;Gain of glycosylation at Y137 (P = 0.046);
MVP
0.98
MPC
0.72
ClinPred
1.0
D
GERP RS
5.3
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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.

Other links and lift over

dbSNP: rs1057519348; hg19: chr4-84200126; API