rs4777

Variant names:

• chr2-73958749-A-T
• rs4777
• NM_080916.3:c.*13A>T

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.245
• Publications: 20 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-AS1 (HGNC:43441): (DGUOK antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 137083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.596 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.*13A>T		3_prime_UTR	Exon 7 of 7	NP_550438.1	E5KSL5
	DGUOK	NM_080918.3		c.*13A>T		3_prime_UTR	Exon 5 of 5	NP_550440.1	Q16854-2
	DGUOK	NM_001318859.2		c.*13A>T		3_prime_UTR	Exon 5 of 5	NP_001305788.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGUOK	ENST00000264093.9	TSL:1 MANE Select	c.*13A>T		3_prime_UTR	Exon 7 of 7	ENSP00000264093.4	Q16854-1
	DGUOK	ENST00000418996.5	TSL:1	n.*200A>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000408209.1	Q16854-6
	DGUOK	ENST00000418996.5	TSL:1	n.*200A>T		3_prime_UTR	Exon 4 of 4	ENSP00000408209.1	Q16854-6

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87200 AN: 151928 Hom.: 25326 Cov.: 32

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

GnomAD2 exomes AF: 0.588 AC: 147753 AN: 251346 AF XY: 0.589

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 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.: 32 AF XY: 0.592 AC XY: 428634 AN XY: 723490

African (AFR) AF: 0.498 AC: 16591 AN: 33314

American (AMR) AF: 0.561 AC: 25088 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 13628 AN: 26082

East Asian (EAS) AF: 0.480 AC: 19055 AN: 39672

South Asian (SAS) AF: 0.563 AC: 48486 AN: 86104

European-Finnish (FIN) AF: 0.711 AC: 37995 AN: 53402

Middle Eastern (MID) AF: 0.522 AC: 3004 AN: 5754

European-Non Finnish (NFE) AF: 0.601 AC: 664191 AN: 1104288

Other (OTH) AF: 0.579 AC: 34770 AN: 60092

GnomAD4 genome AF: 0.574 AC: 87249 AN: 152046 Hom.: 25339 Cov.: 32 AF XY: 0.580 AC XY: 43093 AN XY: 74318

African (AFR) AF: 0.510 AC: 21128 AN: 41468

American (AMR) AF: 0.555 AC: 8484 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2663 AN: 5162

South Asian (SAS) AF: 0.556 AC: 2675 AN: 4814

European-Finnish (FIN) AF: 0.723 AC: 7636 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40849 AN: 67974

Other (OTH) AF: 0.556 AC: 1171 AN: 2106

Alfa AF: 0.590 Hom.: 4928

Bravo AF: 0.557

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) (3)
-	-	1	not provided (1)
-	-	1	Portal hypertension, noncirrhotic (1)
-	-	1	Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.79
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4777; hg19: chr2-74185876; COSMIC: COSV51203699; COSMIC: COSV51203699;