Variant 6-18258391-C-T 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.160G>A(p.Val54Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,458,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

DEK
NM_003472.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

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:

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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=0.2652818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEK	NM_003472.4 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	3/11	ENST00000652689.1	NP_003463.1	P35659-1
DEK	XM_024446544.2 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	3/11		XP_024302312.1
DEK	XM_047419335.1 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	3/9		XP_047275291.1
DEK	NM_001134709.2 linkuse as main transcript	c.146-329G>A		intron_variant			NP_001128181.1	P35659-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEK	ENST00000652689.1 linkuse as main transcript	c.160G>A	p.Val54Met	missense_variant	3/11		NM_003472.4	ENSP00000498653.1		P35659-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250524

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1458930

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725910

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:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Jan 04, 2022

The c.160G>A (p.V54M) alteration is located in exon 3 (coding exon 2) of the DEK gene. This alteration results from a G to A substitution at nucleotide position 160, causing the valine (V) at amino acid position 54 to be replaced by a methionine (M). 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

Pathogenic

0.69

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

L;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.15

Sift

Benign

0.21

T;T

Sift4G

Benign

0.16

T;.

Polyphen

1.0

D;.

Vest4

0.78

MutPred

0.20

Loss of sheet (P = 0.0037);.;

MVP

0.83

MPC

0.47

ClinPred

0.80

GERP RS

5.8

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.063

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over