rs7046290

Variant names:

• chr9-87587662-A-G
• rs7046290
• NM_004938.4:c.63-17292A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004938.4(DAPK1):​c.63-17292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 152,312 control chromosomes in the GnomAD database, including 1,255 homozygotes. 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: 𝑓 0.096 (1255 hom., cov: 33)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

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.63-17292A>G		intron	N/A	NP_004929.2	P53355-1
	DAPK1	NM_001288729.2		c.63-17292A>G		intron	N/A	NP_001275658.1	P53355-1
	DAPK1	NM_001288730.2		c.63-17292A>G		intron	N/A	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.63-17292A>G		intron	N/A	ENSP00000386135.3	P53355-1
	DAPK1	ENST00000358077.9	TSL:1	c.63-17292A>G		intron	N/A	ENSP00000350785.5	P53355-1
	DAPK1	ENST00000472284.5	TSL:1	c.63-17292A>G		intron	N/A	ENSP00000417076.1	P53355-1

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14630 AN: 152194 Hom.: 1255 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0521

Gnomad OTH AF: 0.0731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0962 AC: 14652 AN: 152312 Hom.: 1255 Cov.: 33 AF XY: 0.0921 AC XY: 6863 AN XY: 74488

African (AFR) AF: 0.228 AC: 9479 AN: 41532

American (AMR) AF: 0.0585 AC: 895 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0130 AC: 63 AN: 4832

European-Finnish (FIN) AF: 0.0299 AC: 318 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0521 AC: 3543 AN: 68042

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0614 Hom.: 241

Bravo AF: 0.105

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.28
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs7046290; hg19: chr9-90202577;