6-18256405-T-C

Variant names:

• chr6-18256405-T-C
• rs1041927927
• NM_003472.4:c.408A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003472.4(DEK):​c.408A>G​(p.Glu136Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DEK NM_003472.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=2.87 with no splicing effect.

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.408A>G	p.Glu136Glu	synonymous	Exon 5 of 11	NP_003463.1	P35659-1
	DEK	NM_001134709.2		c.306A>G	p.Glu102Glu	synonymous	Exon 4 of 10	NP_001128181.1	P35659-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEK	ENST00000652689.1	MANE Select	c.408A>G	p.Glu136Glu	synonymous	Exon 5 of 11	ENSP00000498653.1	P35659-1
	DEK	ENST00000852490.1		c.408A>G	p.Glu136Glu	synonymous	Exon 5 of 12	ENSP00000522549.1
	DEK	ENST00000507591.2	TSL:2	c.408A>G	p.Glu136Glu	synonymous	Exon 5 of 10	ENSP00000423427.2	H0Y993

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.8
DANN	Benign	0.60
PhyloP100		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1041927927; hg19: chr6-18256636;