Genetic Variant DCK:c.91+37G>C (chr4-70993963-G-C) – 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.91+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,469,492 control chromosomes in the GnomAD database, including 253 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 0.014 ( 23 hom., cov: 32)

Exomes 𝑓: 0.017 ( 230 hom. )

Consequence

DCK
NM_000788.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.389

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2165/152340) while in subpopulation NFE AF= 0.0197 (1343/68022). AF 95% confidence interval is 0.0189. There are 23 homozygotes in gnomad4. There are 1068 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCK	NM_000788.3 link	c.91+37G>C		intron_variant	Intron 1 of 6	ENST00000286648.10	NP_000779.1	P27707F5CTF3
DCK	XM_047449689.1 link	c.-180G>C		5_prime_UTR_variant	Exon 1 of 7		XP_047305645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCK	ENST00000286648.10 link	c.91+37G>C		intron_variant	Intron 1 of 6	1	NM_000788.3	ENSP00000286648.5		P27707

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2165

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00785

Gnomad FIN

AF:

0.0205

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.0147

AC:

3445

AN:

234998

Hom.:

AF XY:

0.0150

AC XY:

1901

AN XY:

127064

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.00939

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.0000574

Gnomad SAS exome

AF:

0.00676

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0200

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0166

AC:

21845

AN:

1317152

Hom.:

230

Cov.:

AF XY:

0.0164

AC XY:

10859

AN XY:

662174

show subpopulations

Gnomad4 AFR exome

AF:

0.00340

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0209

Gnomad4 EAS exome

AF:

0.0000773

Gnomad4 SAS exome

AF:

0.00727

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0142

AC:

2165

AN:

152340

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1068

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.0142

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0205

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.3

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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