rs763562410
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001358921.2(COQ2):c.1010G>A(p.Arg337Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
COQ2
NM_001358921.2 missense
NM_001358921.2 missense
Scores
4
9
Clinical Significance
Conservation
PhyloP100: 5.87
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36017698).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ2 | NM_001358921.2 | c.1010G>A | p.Arg337Gln | missense_variant | 7/7 | ENST00000647002.2 | |
COQ2 | NM_015697.9 | c.1160G>A | p.Arg387Gln | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ2 | ENST00000647002.2 | c.1010G>A | p.Arg337Gln | missense_variant | 7/7 | NM_001358921.2 | P2 | ||
COQ2 | ENST00000311469.9 | c.1160G>A | p.Arg387Gln | missense_variant | 7/7 | 1 | A2 | ||
COQ2 | ENST00000503915.5 | c.*142G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 1 | ||||
COQ2 | ENST00000503391.5 | c.*176-1650G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000202 AC: 5AN: 247524Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134262
GnomAD3 exomes
AF:
AC:
5
AN:
247524
Hom.:
AF XY:
AC XY:
2
AN XY:
134262
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460074Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 726212
GnomAD4 exome
AF:
AC:
10
AN:
1460074
Hom.:
Cov.:
30
AF XY:
AC XY:
4
AN XY:
726212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 387 of the COQ2 protein (p.Arg387Gln). This variant is present in population databases (rs763562410, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 60539). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COQ2 protein function. Experimental studies have shown that this missense change affects COQ2 function (PMID: 23758206). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Multiple system atrophy Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jul 18, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Vest4
0.48
MutPred
Gain of sheet (P = 0.0827);.;
MVP
0.63
MPC
0.28
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at