2-73926863-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000629438.2(DGUOK):c.-48G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00818 in 1,606,436 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (525 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (424 hom.)
• Consequence: DGUOK ENST00000629438.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-73926863-G-A is Benign according to our data. Variant chr2-73926863-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 137084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DGUOK	NM_080916.3			upstream_gene_variant		ENST00000264093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGUOK	ENST00000264093.9			upstream_gene_variant		1	NM_080916.3	P1

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6751 AN: 151870 Hom.: 523 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000384

Gnomad OTH AF: 0.0234

GnomAD3 exomes AF: 0.0110 AC: 2736 AN: 248708 Hom.: 192 AF XY: 0.00794 AC XY: 1071 AN XY: 134832

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00476

GnomAD4 exome AF: 0.00438 AC: 6372 AN: 1454448 Hom.: 424 Cov.: 32 AF XY: 0.00369 AC XY: 2668 AN XY: 723694

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.00686

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.00930

GnomAD4 genome AF: 0.0445 AC: 6766 AN: 151988 Hom.: 525 Cov.: 33 AF XY: 0.0429 AC XY: 3189 AN XY: 74320

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000384

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00983 Hom.: 93

Bravo AF: 0.0505

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 18, 2011

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mitochondrial DNA depletion syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	14
Dann	Benign	0.95

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

Other links and lift over

dbSNP: rs10186730; hg19: chr2-74153990;