Genetic Variant DGUOK:c.-133C>T (chr2-73926778-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_080916.3(DGUOK):c.-133C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,401,978 control chromosomes in the GnomAD database, including 683,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74637 hom., cov: 34)

Exomes 𝑓: 0.99 ( 609049 hom. )

Consequence

DGUOK
NM_080916.3 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.913

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-73926778-C-T is Benign according to our data. Variant chr2-73926778-C-T is described in ClinVar as [Benign]. Clinvar id is 1294364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGUOK	NM_080916.3 link	c.-133C>T		upstream_gene_variant		ENST00000264093.9	NP_550438.1	Q16854-1E5KSL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9 link	c.-133C>T		upstream_gene_variant		1	NM_080916.3	ENSP00000264093.4		Q16854-1

Frequencies

GnomAD3 genomes

AF:

0.990

AC:

150691

AN:

152268

Hom.:

74578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

0.989

Gnomad AMR

AF:

0.991

Gnomad ASJ

AF:

0.986

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.981

Gnomad NFE

AF:

0.984

Gnomad OTH

AF:

0.991

GnomAD4 exome

AF:

0.987

AC:

1233711

AN:

1249592

Hom.:

609049

Cov.:

AF XY:

0.987

AC XY:

614732

AN XY:

622592

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.994

Gnomad4 ASJ exome

AF:

0.984

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.993

Gnomad4 FIN exome

AF:

0.983

Gnomad4 NFE exome

AF:

0.986

Gnomad4 OTH exome

AF:

0.990

GnomAD4 genome

AF:

0.990

AC:

150809

AN:

152386

Hom.:

74637

Cov.:

AF XY:

0.990

AC XY:

73751

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.991

Gnomad4 ASJ

AF:

0.986

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.995

Gnomad4 FIN

AF:

0.984

Gnomad4 NFE

AF:

0.984

Gnomad4 OTH

AF:

0.991

Alfa

AF:

0.986

Hom.:

10764

Bravo

AF:

0.990

Asia WGS

AF:

0.996

AC:

3465

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.5

DANN

Benign

0.86

Splicing

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