NM_004938.4:c.1825-2617C>T

Variant names:

• chr9-87655412-C-T
• rs943855
• NM_004938.4:c.1825-2617C>T

Variant summary

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

The NM_004938.4(DAPK1):​c.1825-2617C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,822 control chromosomes in the GnomAD database, including 10,382 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 0.34 (10382 hom., cov: 32)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.1825-2617C>T		intron_variant	Intron 17 of 25	ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.1825-2617C>T		intron_variant	Intron 17 of 25	2	NM_004938.4	ENSP00000386135.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52253 AN: 151704 Hom.: 10369 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.344 AC: 52277 AN: 151822 Hom.: 10382 Cov.: 32 AF XY: 0.351 AC XY: 26031 AN XY: 74186

African (AFR) AF: 0.160 AC: 6637 AN: 41408

American (AMR) AF: 0.530 AC: 8096 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 990 AN: 3466

East Asian (EAS) AF: 0.611 AC: 3137 AN: 5136

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4814

European-Finnish (FIN) AF: 0.452 AC: 4756 AN: 10516

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26187 AN: 67914

Other (OTH) AF: 0.363 AC: 760 AN: 2096

Alfa AF: 0.364 Hom.: 7816

Bravo AF: 0.350

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.18
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: rs943855; hg19: chr9-90270327;