rs6546878

Positions:

• chr2-73948197-C-A
• chr2-73948197-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080916.3(DGUOK):​c.443+1291C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,100 control chromosomes in the GnomAD database, including 35,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35234 hom., cov: 32)
• Consequence: DGUOK NM_080916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DGUOK	NM_080916.3	c.443+1291C>A		intron_variant		ENST00000264093.9	NP_550438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9	c.443+1291C>A		intron_variant		1	NM_080916.3	ENSP00000264093.4

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103072 AN: 151982 Hom.: 35207 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.659

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.678 AC: 103152 AN: 152100 Hom.: 35234 Cov.: 32 AF XY: 0.679 AC XY: 50507 AN XY: 74352

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.657

Alfa AF: 0.619 Hom.: 2807

Bravo AF: 0.668

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs6546878; hg19: chr2-74175324;