6-18237383-T-C

Variant names:

• chr6-18237383-T-C
• rs1392472472
• NM_003472.4:c.896A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003472.4(DEK):​c.896A>G​(p.Lys299Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000209 in 1,437,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. K299T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DEK NM_003472.4 missense, splice_region
• Scores: Splicing: ADA: 0.3929
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.09
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3561738).

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.896A>G	p.Lys299Arg	missense splice_region	Exon 8 of 11	NP_003463.1	P35659-1
	DEK	NM_001134709.2		c.794A>G	p.Lys265Arg	missense splice_region	Exon 7 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.896A>G	p.Lys299Arg	missense splice_region	Exon 8 of 11	ENSP00000498653.1	P35659-1
	DEK	ENST00000852490.1		c.920A>G	p.Lys307Arg	missense splice_region	Exon 9 of 12	ENSP00000522549.1
	DEK	ENST00000507591.2	TSL:2	c.896A>G	p.Lys299Arg	missense splice_region	Exon 8 of 10	ENSP00000423427.2	H0Y993

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1437626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 715626

African (AFR) AF: 0.00 AC: 0 AN: 31404

American (AMR) AF: 0.00 AC: 0 AN: 36824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24924

East Asian (EAS) AF: 0.00 AC: 0 AN: 39476

South Asian (SAS) AF: 0.00 AC: 0 AN: 82522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5602

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1106532

Other (OTH) AF: 0.00 AC: 0 AN: 59238

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.41		Loss of methylation at K299 (P = 0.0037)
MVP		0.81
MPC		0.39
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.11
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.39
dbscSNV1_RF	Benign	0.44
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: rs1392472472; hg19: chr6-18237614;