4-83271015-G-C

Variant names:

• chr4-83271015-G-C
• rs4693075
• NM_001358921.2:c.629-1022C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001358921.2(COQ2):​c.629-1022C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,976 control chromosomes in the GnomAD database, including 29,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.62 (29234 hom., cov: 31)
• Consequence: COQ2 NM_001358921.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0270
• Publications: 17 publications found

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]

COQ2 Gene-Disease associations (from GenCC):

• coenzyme Q10 deficiency, primary, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple system atrophy

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• Leigh syndrome with nephrotic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-83271015-G-C is Benign according to our data. Variant chr4-83271015-G-C is described in ClinVar as Benign. ClinVar VariationId is 226000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	NM_001358921.2	MANE Select	c.629-1022C>G		intron	N/A	NP_001345850.1	Q96H96-1
	COQ2	NM_015697.9		c.779-1022C>G		intron	N/A	NP_056512.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	ENST00000647002.2	MANE Select	c.629-1022C>G		intron	N/A	ENSP00000495761.2	Q96H96-1
	COQ2	ENST00000311469.9	TSL:1	c.779-1022C>G		intron	N/A	ENSP00000310873.4	Q96H96-4
	COQ2	ENST00000503915.5	TSL:1	n.320-1022C>G		intron	N/A	ENSP00000427146.1	H0YAI0

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93643 AN: 151858 Hom.: 29223 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.616 AC: 93683 AN: 151976 Hom.: 29234 Cov.: 31 AF XY: 0.624 AC XY: 46379 AN XY: 74292

African (AFR) AF: 0.544 AC: 22536 AN: 41436

American (AMR) AF: 0.621 AC: 9478 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3470

East Asian (EAS) AF: 0.850 AC: 4410 AN: 5186

South Asian (SAS) AF: 0.688 AC: 3316 AN: 4822

European-Finnish (FIN) AF: 0.728 AC: 7663 AN: 10528

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42226 AN: 67956

Other (OTH) AF: 0.599 AC: 1261 AN: 2106

Alfa AF: 0.617 Hom.: 3477

Bravo AF: 0.606

Asia WGS AF: 0.764 AC: 2659 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		-0.027
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4693075; hg19: chr4-84192168;