Variant 6-18237383-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003472.4(DEK):c.896A>C(p.Lys299Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000278 in 1,437,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DEK
NM_003472.4 missense, splice_region

Scores

Splicing: ADA: 0.8210

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

Genes affected

DEK (HGNC:2768): (DEK proto-oncogene) This gene encodes a protein with one SAP domain. This protein binds to cruciform and superhelical DNA and induces positive supercoils into closed circular DNA, and is also involved in splice site selection during mRNA processing. Chromosomal aberrations involving this region, increased expression of this gene, and the presence of antibodies against this protein are all associated with various diseases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

DEK links:

DEK (HGNC:):

DEK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39393544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEK	NM_003472.4 linkuse as main transcript	c.896A>C	p.Lys299Thr	missense_variant, splice_region_variant	8/11	ENST00000652689.1	NP_003463.1	P35659-1
DEK	NM_001134709.2 linkuse as main transcript	c.794A>C	p.Lys265Thr	missense_variant, splice_region_variant	7/10		NP_001128181.1	P35659-2
DEK	XM_024446544.2 linkuse as main transcript	c.896A>C	p.Lys299Thr	missense_variant, splice_region_variant	8/11		XP_024302312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEK	ENST00000652689.1 linkuse as main transcript	c.896A>C	p.Lys299Thr	missense_variant, splice_region_variant	8/11		NM_003472.4	ENSP00000498653.1		P35659-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000440

AC:

AN:

227204

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123644

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1437626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.896A>C (p.K299T) alteration is located in exon 8 (coding exon 7) of the DEK gene. This alteration results from a A to C substitution at nucleotide position 896, causing the lysine (K) at amino acid position 299 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;.

M_CAP

Benign

0.029

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.016

D;D;D

Sift4G

Benign

0.063

T;T;T

Polyphen

1.0

D;.;.

Vest4

0.52

MVP

0.83

MPC

0.49

ClinPred

0.73

GERP RS

5.7

Varity_R

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.82

dbscSNV1_RF

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over