2-73938729-G-A

Variant names:

• chr2-73938729-G-A
• rs831527
• NM_080916.3:c.143-181G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080916.3(DGUOK):​c.143-181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,100 control chromosomes in the GnomAD database, including 24,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24724 hom., cov: 32)
• Consequence: DGUOK NM_080916.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.532

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-73938729-G-A is Benign according to our data. Variant chr2-73938729-G-A is described in ClinVar as [Benign]. Clinvar id is 679277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGUOK	NM_080916.3	c.143-181G>A		intron_variant	Intron 1 of 6	ENST00000264093.9	NP_550438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9	c.143-181G>A		intron_variant	Intron 1 of 6	1	NM_080916.3	ENSP00000264093.4

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84699 AN: 151980 Hom.: 24717 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.541

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 84744 AN: 152100 Hom.: 24724 Cov.: 32 AF XY: 0.564 AC XY: 41904 AN XY: 74358

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.540

Alfa AF: 0.565 Hom.: 3833

Bravo AF: 0.535

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.31

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: rs831527; hg19: chr2-74165856;