chr4-83264242-GTCT-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP3

The NM_001358921.2(COQ2):​c.1070_1072del​(p.Lys357del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000107 in 1,593,514 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β˜…).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

COQ2
NM_001358921.2 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 3.71
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]

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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;
BP3
Nonframeshift variant in repetitive region in NM_001358921.2

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COQ2NM_001358921.2 linkuse as main transcriptc.1070_1072del p.Lys357del inframe_deletion 7/7 ENST00000647002.2 NP_001345850.1
COQ2NM_015697.9 linkuse as main transcriptc.1220_1222del p.Lys407del inframe_deletion 7/7 NP_056512.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COQ2ENST00000647002.2 linkuse as main transcriptc.1070_1072del p.Lys357del inframe_deletion 7/7 NM_001358921.2 ENSP00000495761 P2Q96H96-1
COQ2ENST00000311469.9 linkuse as main transcriptc.1220_1222del p.Lys407del inframe_deletion 7/71 ENSP00000310873 A2Q96H96-4
COQ2ENST00000503915.5 linkuse as main transcriptc.*202_*204del 3_prime_UTR_variant, NMD_transcript_variant 7/71 ENSP00000427146
COQ2ENST00000503391.5 linkuse as main transcriptc.*176-1590_*176-1588del intron_variant, NMD_transcript_variant 2 ENSP00000426242

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151514
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000579
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000373
AC:
9
AN:
241298
Hom.:
0
AF XY:
0.0000229
AC XY:
3
AN XY:
131102
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000521
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000971
AC:
14
AN:
1441882
Hom.:
0
AF XY:
0.00000975
AC XY:
7
AN XY:
717838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000358
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151632
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74068
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Coenzyme Q10 deficiency, primary, 1;C3714927:Multiple system atrophy 1, susceptibility to Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJul 21, 2021- -
Coenzyme Q10 deficiency, primary, 1 Uncertain:1
Uncertain significance, no assertion criteria providedcurationSingHealth Duke-NUS Institute of Precision MedicineJun 07, 2017- -

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: rs765403087; hg19: chr4-84185395; API