GeneBe

rs184770596

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_080916.3(DGUOK):​c.211C>A​(p.Pro71Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P71A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

DGUOK
NM_080916.3 missense

Scores

14
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.42

Publications

4 publications found
Variant links:
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]
DGUOK-AS1 (HGNC:43441): (DGUOK antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.982

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

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DGUOK
NM_080916.3
MANE Select
c.211C>Ap.Pro71Thr
missense
Exon 2 of 7NP_550438.1
DGUOK
NM_080918.3
c.211C>Ap.Pro71Thr
missense
Exon 2 of 5NP_550440.1
DGUOK
NM_001318859.2
c.211C>Ap.Pro71Thr
missense
Exon 2 of 5NP_001305788.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DGUOK
ENST00000264093.9
TSL:1 MANE Select
c.211C>Ap.Pro71Thr
missense
Exon 2 of 7ENSP00000264093.4
DGUOK
ENST00000418996.5
TSL:1
n.143-7741C>A
intron
N/AENSP00000408209.1
DGUOK
ENST00000893377.1
c.211C>Ap.Pro71Thr
missense
Exon 2 of 7ENSP00000563436.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.58
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.97
D
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.49
D
MetaRNN
Pathogenic
0.98
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.9
H
PhyloP100
7.4
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-7.6
D
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.98
D
Vest4
0.94
MutPred
0.81
Loss of sheet (P = 0.0063)
MVP
1.0
MPC
0.46
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.95
gMVP
0.77
Mutation Taster
=33/67
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs184770596; hg19: chr2-74166105; API