rs6535454
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001358921.2(COQ2):c.744T>C(p.Asp248=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,598,806 control chromosomes in the GnomAD database, including 415,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.75 ( 42874 hom., cov: 32)
Exomes 𝑓: 0.72 ( 372150 hom. )
Consequence
COQ2
NM_001358921.2 synonymous
NM_001358921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.24
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 4-83269878-A-G is Benign according to our data. Variant chr4-83269878-A-G is described in ClinVar as [Benign]. Clinvar id is 128829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-83269878-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.24 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ2 | NM_001358921.2 | c.744T>C | p.Asp248= | synonymous_variant | 5/7 | ENST00000647002.2 | |
COQ2 | NM_015697.9 | c.894T>C | p.Asp298= | synonymous_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ2 | ENST00000647002.2 | c.744T>C | p.Asp248= | synonymous_variant | 5/7 | NM_001358921.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.749 AC: 113854AN: 152024Hom.: 42844 Cov.: 32
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GnomAD3 exomes AF: 0.735 AC: 177117AN: 240834Hom.: 65446 AF XY: 0.735 AC XY: 96265AN XY: 131044
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GnomAD4 exome AF: 0.716 AC: 1035979AN: 1446664Hom.: 372150 Cov.: 32 AF XY: 0.718 AC XY: 516508AN XY: 719836
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GnomAD4 genome ? AF: 0.749 AC: 113936AN: 152142Hom.: 42874 Cov.: 32 AF XY: 0.754 AC XY: 56071AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 01, 2011 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jul 15, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 88. Only high quality variants are reported. - |
Coenzyme Q10 deficiency, primary, 1 Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 11, 2016 | - - |
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