chr2-73938926-G-A

Position:

chr2-73938926-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_080916.3(DGUOK):c.159G>A(p.Thr53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 1,613,022 control chromosomes in the GnomAD database, including 574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 30 hom., cov: 32)

Exomes 𝑓: 0.024 ( 544 hom. )

Consequence

DGUOK
NM_080916.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0730

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 2-73938926-G-A is Benign according to our data. Variant chr2-73938926-G-A is described in ClinVar as [Benign]. Clinvar id is 137080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-73938926-G-A is described in Lovd as [Benign]. Variant chr2-73938926-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0169 (2574/152262) while in subpopulation NFE AF= 0.0279 (1897/68020). AF 95% confidence interval is 0.0268. There are 30 homozygotes in gnomad4. There are 1201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGUOK	NM_080916.3 linkuse as main transcript	c.159G>A	p.Thr53=	synonymous_variant	2/7	ENST00000264093.9	NP_550438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9 linkuse as main transcript	c.159G>A	p.Thr53=	synonymous_variant	2/7	1	NM_080916.3	ENSP00000264093	P1	Q16854-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2576

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00442

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0279

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0187

AC:

4702

AN:

251468

Hom.:

AF XY:

0.0190

AC XY:

2587

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00511

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0301

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0245

AC:

35717

AN:

1460760

Hom.:

544

Cov.:

AF XY:

0.0239

AC XY:

17370

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.00442

Gnomad4 AMR exome

AF:

0.00608

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0286

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0169

AC:

2574

AN:

152262

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1201

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00440

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0220

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0239

EpiControl

AF:

0.0226

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 26, 2016	- -

Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over