Variant 6-18249706-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003472.4(DEK):c.707A>G(p.Glu236Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000741 in 1,605,770 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 3 hom. )

Consequence

DEK
NM_003472.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.074698776).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEK	NM_003472.4 linkuse as main transcript	c.707A>G	p.Glu236Gly	missense_variant	7/11	ENST00000652689.1	NP_003463.1	P35659-1
DEK	NM_001134709.2 linkuse as main transcript	c.605A>G	p.Glu202Gly	missense_variant	6/10		NP_001128181.1	P35659-2
DEK	XM_024446544.2 linkuse as main transcript	c.707A>G	p.Glu236Gly	missense_variant	7/11		XP_024302312.1
DEK	XM_047419335.1 linkuse as main transcript	c.707A>G	p.Glu236Gly	missense_variant	7/9		XP_047275291.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEK	ENST00000652689.1 linkuse as main transcript	c.707A>G	p.Glu236Gly	missense_variant	7/11		NM_003472.4	ENSP00000498653.1		P35659-1

Frequencies

GnomAD3 genomes

AF:

0.000571

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000433

AC:

105

AN:

242420

Hom.:

AF XY:

0.000474

AC XY:

AN XY:

130748

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000682

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000723

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000691

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000759

AC:

1103

AN:

1453538

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

520

AN XY:

722600

show subpopulations

Gnomad4 AFR exome

AF:

0.0000911

Gnomad4 AMR exome

AF:

0.000563

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000926

Gnomad4 OTH exome

AF:

0.000615

GnomAD4 genome

AF:

0.000571

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000579

Hom.:

Bravo

AF:

0.000612

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000329

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

Oct 06, 2024

The c.707A>G (p.E236G) alteration is located in exon 7 (coding exon 6) of the DEK gene. This alteration results from a A to G substitution at nucleotide position 707, causing the glutamic acid (E) at amino acid position 236 to be replaced by a glycine (G). 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

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.87

D;D;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.075

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;N;D

REVEL

Benign

0.12

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.11

T;D;D

Polyphen

0.46

P;.;.

Vest4

0.41

MVP

0.81

MPC

0.49

ClinPred

0.14

GERP RS

5.0

Varity_R

0.22

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