4-83264146-C-T

Position:

• chr4-83264146-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001358921.2(COQ2):​c.*53G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 922,188 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 32)
  • Exomes 𝑓: 0.012 (70 hom.)
• Consequence: COQ2 NM_001358921.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 4-83264146-C-T is Benign according to our data. Variant chr4-83264146-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 349911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1660/152222) while in subpopulation NFE AF= 0.0149 (1011/68016). AF 95% confidence interval is 0.0141. There are 17 homozygotes in gnomad4. There are 864 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ2	NM_001358921.2	c.*53G>A		3_prime_UTR_variant	7/7	ENST00000647002.2	NP_001345850.1
COQ2	NM_015697.9	c.*53G>A		3_prime_UTR_variant	7/7		NP_056512.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ2	ENST00000647002.2	c.*53G>A		3_prime_UTR_variant	7/7		NM_001358921.2	ENSP00000495761	P2
COQ2	ENST00000311469.9	c.*53G>A		3_prime_UTR_variant	7/7	1		ENSP00000310873	A2
COQ2	ENST00000503915.5	c.*301G>A		3_prime_UTR_variant, NMD_transcript_variant	7/7	1		ENSP00000427146
COQ2	ENST00000503391.5	c.*176-1491G>A		intron_variant, NMD_transcript_variant		2		ENSP00000426242

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1661 AN: 152106 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00963

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.0115 AC: 8892 AN: 769966 Hom.: 70 Cov.: 10 AF XY: 0.0114 AC XY: 4515 AN XY: 396654

Gnomad4 AFR exome AF: 0.00256

Gnomad4 AMR exome AF: 0.00785

Gnomad4 ASJ exome AF: 0.00354

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00447

Gnomad4 FIN exome AF: 0.0327

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.00958

GnomAD4 genome AF: 0.0109 AC: 1660 AN: 152222 Hom.: 17 Cov.: 32 AF XY: 0.0116 AC XY: 864 AN XY: 74406

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00962

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.0320

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.0145 Hom.: 6

Bravo AF: 0.00864

Asia WGS AF: 0.00145 AC: 5 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.0
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs143771689; hg19: chr4-84185299;