4-83263850-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The NM_001358921.2(COQ2):​c.*348dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 156,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

COQ2
NM_001358921.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.620
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000204 (31/152048) while in subpopulation AMR AF= 0.00072 (11/15274). AF 95% confidence interval is 0.000403. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COQ2NM_001358921.2 linkc.*348dupT 3_prime_UTR_variant Exon 7 of 7 ENST00000647002.2 NP_001345850.1
COQ2NM_015697.9 linkc.*348dupT 3_prime_UTR_variant Exon 7 of 7 NP_056512.5 Q96H96-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COQ2ENST00000647002 linkc.*348dupT 3_prime_UTR_variant Exon 7 of 7 NM_001358921.2 ENSP00000495761.2 Q96H96-1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
151930
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000721
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00108
AC:
5
AN:
4622
Hom.:
0
Cov.:
0
AF XY:
0.00157
AC XY:
4
AN XY:
2542
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00316
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00116
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152048
Hom.:
0
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000720
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000336

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Coenzyme Q10 deficiency Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs542593202; hg19: chr4-84185003; API