ENST00000629438:c.-60_-57dupGCGA

Variant names:

• chr2-73926849-C-CAGCG
• rs567251538
• ENST00000629438:c.-60_-57dupGCGA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000629438(DGUOK):​c.-60_-57dupGCGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,609,590 control chromosomes in the GnomAD database, including 25 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (23 hom.)
• Consequence: DGUOK ENST00000629438 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.46

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00302 (460/152362) while in subpopulation NFE AF= 0.00453 (308/68026). AF 95% confidence interval is 0.00411. There are 2 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGUOK	NM_080916.3	c.-62_-61insAGCG		upstream_gene_variant		ENST00000264093.9	NP_550438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGUOK	ENST00000264093.9	c.-62_-61insAGCG		upstream_gene_variant		1	NM_080916.3	ENSP00000264093.4

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 460 AN: 152244 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00453

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00417 AC: 6083 AN: 1457228 Hom.: 23 Cov.: 32 AF XY: 0.00408 AC XY: 2959 AN XY: 725066

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00107

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000487

Gnomad4 FIN exome AF: 0.00847

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00307

GnomAD4 genome AF: 0.00302 AC: 460 AN: 152362 Hom.: 2 Cov.: 33 AF XY: 0.00299 AC XY: 223 AN XY: 74506

Gnomad4 AFR AF: 0.000793

Gnomad4 AMR AF: 0.00183

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.00453

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00367 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial DNA depletion syndrome Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs567251538; hg19: chr2-74153976;