chr4-83267697-G-A

Variant names:

• chr4-83267697-G-A
• rs1129617
• NM_001358921.2:c.840C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015697.9(COQ2):​c.990C>T​(p.Ser330Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,554,922 control chromosomes in the GnomAD database, including 57,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4329 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53542 hom.)
• Consequence: COQ2 NM_015697.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.249
• Publications: 24 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: Labcorp Genetics (formerly Invitae), G2P
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-83267697-G-A is Benign according to our data. Variant chr4-83267697-G-A is described in ClinVar as Benign. ClinVar VariationId is 128830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.249 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015697.9. 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.840C>T	p.Ser280Ser	synonymous	Exon 6 of 7	NP_001345850.1
	COQ2	NM_015697.9		c.990C>T	p.Ser330Ser	synonymous	Exon 6 of 7	NP_056512.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ2	ENST00000647002.2	MANE Select	c.840C>T	p.Ser280Ser	synonymous	Exon 6 of 7	ENSP00000495761.2
	COQ2	ENST00000311469.9	TSL:1	c.990C>T	p.Ser330Ser	synonymous	Exon 6 of 7	ENSP00000310873.4
	COQ2	ENST00000503915.5	TSL:1	n.531C>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000427146.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34770 AN: 151906 Hom.: 4322 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.258 AC: 42199 AN: 163364 AF XY: 0.262

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.286

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.280

GnomAD4 exome AF: 0.273 AC: 383173 AN: 1402898 Hom.: 53542 Cov.: 33 AF XY: 0.273 AC XY: 189276 AN XY: 692402

African (AFR) AF: 0.133 AC: 4214 AN: 31702

American (AMR) AF: 0.290 AC: 10410 AN: 35958

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 8106 AN: 25198

East Asian (EAS) AF: 0.138 AC: 4954 AN: 35914

South Asian (SAS) AF: 0.282 AC: 22358 AN: 79320

European-Finnish (FIN) AF: 0.211 AC: 10487 AN: 49714

Middle Eastern (MID) AF: 0.302 AC: 1712 AN: 5664

European-Non Finnish (NFE) AF: 0.282 AC: 305383 AN: 1081152

Other (OTH) AF: 0.267 AC: 15549 AN: 58276

GnomAD4 genome AF: 0.229 AC: 34809 AN: 152024 Hom.: 4329 Cov.: 32 AF XY: 0.226 AC XY: 16780 AN XY: 74300

African (AFR) AF: 0.137 AC: 5660 AN: 41458

American (AMR) AF: 0.271 AC: 4136 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3470

East Asian (EAS) AF: 0.134 AC: 692 AN: 5160

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2099 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18911 AN: 67964

Other (OTH) AF: 0.249 AC: 525 AN: 2108

Alfa AF: 0.257 Hom.: 3193

Bravo AF: 0.230

Asia WGS AF: 0.200 AC: 692 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	2	Coenzyme Q10 deficiency, primary, 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.80
PhyloP100		-0.25
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: rs1129617; hg19: chr4-84188850; COSMIC: COSV61021267;