4-83264271-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001358921.2(COQ2):c.1044C>T(p.Val348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000937 in 1,610,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
COQ2
NM_001358921.2 synonymous
NM_001358921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0850
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 Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 4-83264271-G-A is Benign according to our data. Variant chr4-83264271-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 384976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.085 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COQ2 | NM_001358921.2 | c.1044C>T | p.Val348= | synonymous_variant | 7/7 | ENST00000647002.2 | NP_001345850.1 | |
COQ2 | NM_015697.9 | c.1194C>T | p.Val398= | synonymous_variant | 7/7 | NP_056512.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COQ2 | ENST00000647002.2 | c.1044C>T | p.Val348= | synonymous_variant | 7/7 | NM_001358921.2 | ENSP00000495761 | P2 | ||
COQ2 | ENST00000311469.9 | c.1194C>T | p.Val398= | synonymous_variant | 7/7 | 1 | ENSP00000310873 | A2 | ||
COQ2 | ENST00000503915.5 | c.*176C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 1 | ENSP00000427146 | ||||
COQ2 | ENST00000503391.5 | c.*176-1616C>T | intron_variant, NMD_transcript_variant | 2 | ENSP00000426242 |
Frequencies
GnomAD3 genomes AF: 0.000541 AC: 82AN: 151476Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000117 AC: 29AN: 246928Hom.: 0 AF XY: 0.0000746 AC XY: 10AN XY: 134084
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GnomAD4 exome AF: 0.0000473 AC: 69AN: 1459114Hom.: 0 Cov.: 30 AF XY: 0.0000455 AC XY: 33AN XY: 725836
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GnomAD4 genome AF: 0.000541 AC: 82AN: 151592Hom.: 0 Cov.: 32 AF XY: 0.000513 AC XY: 38AN XY: 74024
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ClinVar
Significance: Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | COQ2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | - - |
Coenzyme Q10 deficiency, primary, 1;C3714927:Multiple system atrophy 1, susceptibility to Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 20, 2021 | - - |
COQ2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at