rs1803484

Positions:

• chr4-71030626-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000788.3(DCK):​c.*1248A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 152,224 control chromosomes in the GnomAD database, including 55 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 0.021 (55 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: DCK NM_000788.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

Genes affected

DCK (HGNC:2704): (deoxycytidine kinase) Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased deoxycytidine kinase activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0214 (3256/152224) while in subpopulation NFE AF= 0.0342 (2322/67976). AF 95% confidence interval is 0.033. There are 55 homozygotes in gnomad4. There are 1511 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCK	NM_000788.3	c.*1248A>G		3_prime_UTR_variant	7/7	ENST00000286648.10	NP_000779.1
DCK	XM_047449689.1	c.*1248A>G		3_prime_UTR_variant	7/7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10	c.*1248A>G		3_prime_UTR_variant	7/7	1	NM_000788.3	ENSP00000286648.5

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3256 AN: 152106 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.00521

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0214 AC: 3256 AN: 152224 Hom.: 55 Cov.: 33 AF XY: 0.0203 AC XY: 1511 AN XY: 74440

Gnomad4 AFR AF: 0.00520

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0342

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0299 Hom.: 21

Bravo AF: 0.0188

Asia WGS AF: 0.00321 AC: 11 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.9
DANN	Benign	0.84

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: rs1803484; hg19: chr4-71896343;