rs368507578
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001358921.2(COQ2):c.189G>T(p.Val63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,553,630 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0065 ( 11 hom., cov: 34)
Exomes 𝑓: 0.00066 ( 6 hom. )
Consequence
COQ2
NM_001358921.2 synonymous
NM_001358921.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.63
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=-0.61).
BP6
?
Variant 4-83284576-C-A is Benign according to our data. Variant chr4-83284576-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 136980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.63 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00652 (992/152178) while in subpopulation AFR AF= 0.0224 (929/41552). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COQ2 | NM_001358921.2 | c.189G>T | p.Val63= | synonymous_variant | 1/7 | ENST00000647002.2 | |
COQ2 | NM_015697.9 | c.339G>T | p.Val113= | synonymous_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COQ2 | ENST00000647002.2 | c.189G>T | p.Val63= | synonymous_variant | 1/7 | NM_001358921.2 | P2 | ||
COQ2 | ENST00000311469.9 | c.339G>T | p.Val113= | synonymous_variant | 1/7 | 1 | A2 | ||
COQ2 | ENST00000311461.7 | c.189G>T | p.Val63= | synonymous_variant | 1/7 | 5 | |||
COQ2 | ENST00000503391.5 | c.189G>T | p.Val63= | synonymous_variant, NMD_transcript_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00652 AC: 992AN: 152066Hom.: 11 Cov.: 34
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GnomAD3 exomes AF: 0.00109 AC: 159AN: 145330Hom.: 2 AF XY: 0.000813 AC XY: 65AN XY: 79968
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GnomAD4 exome AF: 0.000664 AC: 930AN: 1401452Hom.: 6 Cov.: 84 AF XY: 0.000603 AC XY: 418AN XY: 692790
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2013 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Focal segmental glomerulosclerosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 13, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at