9-87642034-G-A

Variant names:

• chr9-87642034-G-A
• rs200137928
• NM_004938.4:c.894G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004938.4(DAPK1):​c.894G>A​(p.Lys298Lys) variant causes a synonymous change. 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: DAPK1 NM_004938.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95
• Publications: 0 publications found

Genes affected

DAPK1 (HGNC:2674): (death associated protein kinase 1) Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

DAPK1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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 (BayesDel_noAF=-0.24).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004938.4. 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
	DAPK1	NM_004938.4	MANE Select	c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	NP_004929.2	P53355-1
	DAPK1	NM_001288729.2		c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	NP_001275658.1	P53355-1
	DAPK1	NM_001288730.2		c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	NP_001275659.1	P53355-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAPK1	ENST00000408954.8	TSL:2 MANE Select	c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	ENSP00000386135.3	P53355-1
	DAPK1	ENST00000358077.9	TSL:1	c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	ENSP00000350785.5	P53355-1
	DAPK1	ENST00000472284.5	TSL:1	c.894G>A	p.Lys298Lys	synonymous	Exon 10 of 26	ENSP00000417076.1	P53355-1

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	-0.24
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs200137928; hg19: chr9-90256949; COSMIC: COSV63792480; COSMIC: COSV63792480;