rs184770596

Variant names:

• chr2-73938978-C-A
• rs184770596
• NM_080916.3:c.211C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-73938978-C-A
• chr2-73938978-C-G
• chr2-73938978-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM1 PM2 PP3_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.42
• Publications: 4 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]

DGUOK-AS1 (HGNC:43441): (DGUOK antisense RNA 1)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PM1: In a chain Deoxyguanosine kinase, mitochondrial (size 237) in uniprot entity DGUOK_HUMAN there are 16 pathogenic changes around while only 4 benign (80%) in NM_080916.3
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGUOK	NM_080916.3	c.211C>A	p.Pro71Thr	missense_variant	Exon 2 of 7	ENST00000264093.9	NP_550438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9	c.211C>A	p.Pro71Thr	missense_variant	Exon 2 of 7	1	NM_080916.3	ENSP00000264093.4

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 v4.3

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;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.9	H;H
PhyloP100		7.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-7.6	D;D
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;.
Vest4		0.94
MutPred		0.81		Loss of sheet (P = 0.0063);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

Other links and lift over

dbSNP: rs184770596; hg19: chr2-74166105;