rs831527

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 VariationId 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.

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	NM_080916.3	MANE Select	c.143-181G>A		intron	N/A	NP_550438.1	E5KSL5
	DGUOK	NM_080918.3		c.143-181G>A		intron	N/A	NP_550440.1	Q16854-2
	DGUOK	NM_001318859.2		c.143-181G>A		intron	N/A	NP_001305788.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGUOK	ENST00000264093.9	TSL:1 MANE Select	c.143-181G>A		intron	N/A	ENSP00000264093.4	Q16854-1
	DGUOK	ENST00000418996.5	TSL:1	n.143-7990G>A		intron	N/A	ENSP00000408209.1	Q16854-6
	DGUOK	ENST00000893377.1		c.143-181G>A		intron	N/A	ENSP00000563436.1

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

African (AFR) AF: 0.388 AC: 16073 AN: 41454

American (AMR) AF: 0.564 AC: 8626 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2013 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2605 AN: 5174

South Asian (SAS) AF: 0.568 AC: 2741 AN: 4824

European-Finnish (FIN) AF: 0.734 AC: 7772 AN: 10588

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43025 AN: 67980

Other (OTH) AF: 0.540 AC: 1141 AN: 2114

Alfa AF: 0.560 Hom.: 3894

Bravo AF: 0.535

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.31
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs831527; hg19: chr2-74165856;