2-73926778-C-T

Variant summary

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

The 2-73926778-C-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 ENST00000629438.2 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.913

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=-0.74).
• 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_single_submitter, 1 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DGUOK	ENST00000629438.2			upstream_gene_variant		1
DGUOK	ENST00000348222.3			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150691 AN: 152268 Hom.: 74578 Cov.: 34

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.: 18 AF XY: 0.987 AC XY: 614732 AN XY: 622592

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.: 34 AF XY: 0.990 AC XY: 73751 AN XY: 74518

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs831526; hg19: chr2-74153905;