Genetic Variant DEK:p.Gly27Arg (chr6-18263909-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003472.4(DEK):c.79G>C(p.Gly27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G27S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

DEK
NM_003472.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11813703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003472.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEK	NM_003472.4	MANE Select	c.79G>C	p.Gly27Arg	missense	Exon 2 of 11	NP_003463.1	P35659-1
	DEK	NM_001134709.2		c.79G>C	p.Gly27Arg	missense	Exon 2 of 10	NP_001128181.1	P35659-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEK	ENST00000652689.1	MANE Select	c.79G>C	p.Gly27Arg	missense	Exon 2 of 11	ENSP00000498653.1	P35659-1
DEK	ENST00000852490.1		c.79G>C	p.Gly27Arg	missense	Exon 2 of 12	ENSP00000522549.1
DEK	ENST00000507591.2	TSL:2	c.79G>C	p.Gly27Arg	missense	Exon 2 of 10	ENSP00000423427.2	H0Y993

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246676

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1459756

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111030

Other (OTH)

AF:

0.00

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000197

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.82

REVEL

Benign

0.072

Sift

Benign

0.040

Sift4G

Benign

0.31

Polyphen

0.31

Vest4

0.42

MutPred

0.26

Gain of solvent accessibility (P = 0.0971)

MVP

0.68

MPC

0.34

ClinPred

0.27

GERP RS

3.9

PromoterAI

0.018

Neutral

(source)

Varity_R

0.066

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over