rs831526

Variant names:

• chr2-73926778-C-T
• rs831526
• NM_080916.3:c.-133C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-73926778-C-T
• chr2-73926778-C-A
• chr2-73926778-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.913
• Publications: 7 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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome 3 (hepatocerebral type)

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• portal hypertension, noncirrhotic

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.-133C>T		upstream_gene	N/A	NP_550438.1	E5KSL5
	DGUOK	NM_080918.3		c.-133C>T		upstream_gene	N/A	NP_550440.1	Q16854-2
	DGUOK	NM_001318859.2		c.-133C>T		upstream_gene	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.-133C>T		upstream_gene	N/A	ENSP00000264093.4	Q16854-1
	DGUOK	ENST00000418996.5	TSL:1	n.-133C>T		upstream_gene	N/A	ENSP00000408209.1	Q16854-6
	DGUOK	ENST00000893377.1		c.-133C>T		upstream_gene	N/A	ENSP00000563436.1

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

African (AFR) AF: 0.998 AC: 29028 AN: 29086

American (AMR) AF: 0.994 AC: 36502 AN: 36734

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 23765 AN: 24156

East Asian (EAS) AF: 1.00 AC: 35475 AN: 35478

South Asian (SAS) AF: 0.993 AC: 77017 AN: 77554

European-Finnish (FIN) AF: 0.983 AC: 35695 AN: 36304

Middle Eastern (MID) AF: 0.984 AC: 4575 AN: 4648

European-Non Finnish (NFE) AF: 0.986 AC: 938987 AN: 952412

Other (OTH) AF: 0.990 AC: 52667 AN: 53220

GnomAD4 genome AF: 0.990 AC: 150809 AN: 152386 Hom.: 74637 Cov.: 34 AF XY: 0.990 AC XY: 73751 AN XY: 74518

African (AFR) AF: 0.997 AC: 41487 AN: 41596

American (AMR) AF: 0.991 AC: 15182 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3423 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5186 AN: 5186

South Asian (SAS) AF: 0.995 AC: 4804 AN: 4830

European-Finnish (FIN) AF: 0.984 AC: 10457 AN: 10624

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.984 AC: 66984 AN: 68046

Other (OTH) AF: 0.991 AC: 2096 AN: 2114

Alfa AF: 0.986 Hom.: 10764

Bravo AF: 0.990

Asia WGS AF: 0.996 AC: 3465 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.86
PhyloP100		-0.91
PromoterAI		0.084	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs831526; hg19: chr2-74153905;