rs4777

Positions:

chr2-73958749-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080916.3(DGUOK):c.*13A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,605,462 control chromosomes in the GnomAD database, including 283,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25339 hom., cov: 32)

Exomes 𝑓: 0.59 ( 257934 hom. )

Consequence

DGUOK
NM_080916.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.245

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:

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

DGUOK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-73958749-A-T is Benign according to our data. Variant chr2-73958749-A-T is described in ClinVar as [Benign]. Clinvar id is 137083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-73958749-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGUOK	NM_080916.3 linkuse as main transcript	c.*13A>T		3_prime_UTR_variant	7/7	ENST00000264093.9	NP_550438.1
DGUOK-AS1	NR_104030.1 linkuse as main transcript	n.306-542T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9 linkuse as main transcript	c.*13A>T		3_prime_UTR_variant	7/7	1	NM_080916.3	ENSP00000264093	P1	Q16854-1
DGUOK-AS1	ENST00000667561.3 linkuse as main transcript	n.308-10814T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87200

AN:

151928

Hom.:

25326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.751

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.723

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.588

AC:

147753

AN:

251346

Hom.:

43825

AF XY:

0.589

AC XY:

79950

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.529

Gnomad EAS exome

AF:

0.533

Gnomad SAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.719

Gnomad NFE exome

AF:

0.605

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.594

AC:

862808

AN:

1453416

Hom.:

257934

Cov.:

AF XY:

0.592

AC XY:

428634

AN XY:

723490

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.523

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.711

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.579

GnomAD4 genome

AF:

0.574

AC:

87249

AN:

152046

Hom.:

25339

Cov.:

AF XY:

0.580

AC XY:

43093

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.510

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.523

Gnomad4 EAS

AF:

0.516

Gnomad4 SAS

AF:

0.556

Gnomad4 FIN

AF:

0.723

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.556

Alfa

AF:

0.590

Hom.:

4928

Bravo

AF:

0.557

Asia WGS

AF:

0.551

AC:

1916

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 27, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 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 3 (hepatocerebral type)

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Portal hypertension, noncirrhotic

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.3

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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