rs886037613
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.255delA(p.Ala86ProfsTer13) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DGUOK
NM_080916.3 frameshift, splice_region
NM_080916.3 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.483
Publications
2 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 2-73939017-CA-C is Pathogenic according to our data. Variant chr2-73939017-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 8153.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.255delA | p.Ala86ProfsTer13 | frameshift splice_region | Exon 2 of 7 | NP_550438.1 | E5KSL5 | ||
| DGUOK | c.255delA | p.Ala86ProfsTer13 | frameshift splice_region | Exon 2 of 5 | NP_550440.1 | Q16854-2 | |||
| DGUOK | c.255delA | p.Ala86ProfsTer13 | frameshift splice_region | Exon 2 of 5 | NP_001305788.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DGUOK | TSL:1 MANE Select | c.244delA | p.Gly82ProfsTer13 | frameshift | Exon 2 of 7 | ENSP00000264093.4 | Q16854-1 | ||
| DGUOK | TSL:1 | n.143-7708delA | intron | N/A | ENSP00000408209.1 | Q16854-6 | |||
| DGUOK | c.244delA | p.Gly82ProfsTer13 | frameshift | Exon 2 of 7 | ENSP00000563436.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460436Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726646
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1460436
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
726646
African (AFR)
AF:
AC:
0
AN:
33448
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26120
East Asian (EAS)
AF:
AC:
0
AN:
39678
South Asian (SAS)
AF:
AC:
0
AN:
86220
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1110728
Other (OTH)
AF:
AC:
0
AN:
60352
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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