rs886037615
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_080916.3(DGUOK):c.609_610delGT(p.Tyr204ProfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000342 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L203L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
DGUOK
NM_080916.3 frameshift
NM_080916.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.29
Publications
1 publications found
Genes affected
DGUOK (HGNC:2858): (deoxyguanosine kinase) In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by two deoxyribonucleoside kinases, cytosolic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. The protein encoded by this gene is responsible for phosphorylation of purine deoxyribonucleosides in the mitochondrial matrix. In addition, this protein phosphorylates several purine deoxyribonucleoside analogs used in the treatment of lymphoproliferative disorders, and this phosphorylation is critical for the effectiveness of the analogs. Alternative splice variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-73957140-CTG-C is Pathogenic according to our data. Variant chr2-73957140-CTG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 8156.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_080916.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DGUOK | MANE Select | c.609_610delGT | p.Tyr204ProfsTer11 | frameshift | Exon 5 of 7 | NP_550438.1 | E5KSL5 | ||
| DGUOK | c.318_319delGT | p.Tyr107ProfsTer11 | frameshift | Exon 4 of 6 | NP_001305789.1 | ||||
| DGUOK | c.318_319delGT | p.Tyr107ProfsTer11 | frameshift | Exon 5 of 7 | NP_001305790.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DGUOK | TSL:1 MANE Select | c.609_610delGT | p.Tyr204ProfsTer11 | frameshift | Exon 5 of 7 | ENSP00000264093.4 | Q16854-1 | ||
| DGUOK | TSL:1 | n.*61-1004_*61-1003delGT | intron | N/A | ENSP00000408209.1 | Q16854-6 | |||
| DGUOK | c.591_592delGT | p.Tyr198ProfsTer11 | frameshift | Exon 5 of 7 | ENSP00000563436.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461636Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727140 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461636
Hom.:
AF XY:
AC XY:
2
AN XY:
727140
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111850
Other (OTH)
AF:
AC:
5
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.445
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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