rs729958

Variant names:

• chr9-87672272-T-C
• rs729958
• NM_004938.4:c.2001+3598T>C

Variant summary

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

The NM_004938.4(DAPK1):​c.2001+3598T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,032 control chromosomes in the GnomAD database, including 17,306 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 0.44 (17306 hom., cov: 32)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.2001+3598T>C		intron_variant	Intron 19 of 25	ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.2001+3598T>C		intron_variant	Intron 19 of 25	2	NM_004938.4	ENSP00000386135.3

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67382 AN: 151914 Hom.: 17298 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.443 AC: 67396 AN: 152032 Hom.: 17306 Cov.: 32 AF XY: 0.447 AC XY: 33228 AN XY: 74294

African (AFR) AF: 0.164 AC: 6810 AN: 41474

American (AMR) AF: 0.545 AC: 8331 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1976 AN: 3466

East Asian (EAS) AF: 0.494 AC: 2553 AN: 5166

South Asian (SAS) AF: 0.627 AC: 3024 AN: 4824

European-Finnish (FIN) AF: 0.522 AC: 5504 AN: 10550

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37534 AN: 67970

Other (OTH) AF: 0.468 AC: 985 AN: 2104

Alfa AF: 0.484 Hom.: 2406

Bravo AF: 0.431

Asia WGS AF: 0.558 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.56
PhyloP100		0.22
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: rs729958; hg19: chr9-90287187;