dbSNP rs66878317: DCK:p.Ile24Val (chr4-70993905-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000788.3(DCK):c.70A>G(p.Ile24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,696 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0074 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 19 hom. )

Consequence

DCK
NM_000788.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.414

Variant links:

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]

DCK links:

MOB1B (HGNC:29801): (MOB kinase activator 1B) The protein encoded by this gene is similar to the yeast Mob1 protein. Yeast Mob1 binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

MOB1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063028336).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00743 (1131/152240) while in subpopulation AFR AF= 0.0263 (1092/41548). AF 95% confidence interval is 0.025. There are 13 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3 link	c.70A>G	p.Ile24Val	missense_variant	Exon 1 of 7	ENST00000286648.10	NP_000779.1	P27707F5CTF3
DCK	XM_047449689.1 link	c.-238A>G		upstream_gene_variant			XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10 link	c.70A>G	p.Ile24Val	missense_variant	Exon 1 of 7	1	NM_000788.3	ENSP00000286648.5		P27707

Frequencies

GnomAD3 genomes

AF:

0.00738

AC:

1123

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00191

AC:

478

AN:

250860

Hom.:

AF XY:

0.00144

AC XY:

196

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000783

AC:

1144

AN:

1461456

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

490

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0269

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00194

GnomAD4 genome

AF:

0.00743

AC:

1131

AN:

152240

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

545

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000837

Hom.:

Bravo

AF:

0.00790

ESP6500AA

AF:

0.0209

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00244

AC:

296

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.10

T;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.88

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.0

L;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.29

N;N;N

REVEL

Benign

0.27

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.27

MVP

0.67

MPC

0.31

ClinPred

0.015

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over