rs928114

Variant names:

• chr9-87563891-C-G
• rs928114
• NM_004938.4:c.63-41063C>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.63-41063C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,180 control chromosomes in the GnomAD database, including 1,341 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 0.12 (1341 hom., cov: 33)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.63-41063C>G		intron_variant	Intron 2 of 25	ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.63-41063C>G		intron_variant	Intron 2 of 25	2	NM_004938.4	ENSP00000386135.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17785 AN: 152064 Hom.: 1342 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.117 AC: 17781 AN: 152180 Hom.: 1341 Cov.: 33 AF XY: 0.120 AC XY: 8958 AN XY: 74372

African (AFR) AF: 0.0280 AC: 1163 AN: 41536

American (AMR) AF: 0.159 AC: 2430 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.138 AC: 716 AN: 5178

South Asian (SAS) AF: 0.155 AC: 749 AN: 4818

European-Finnish (FIN) AF: 0.185 AC: 1955 AN: 10578

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9972 AN: 67998

Other (OTH) AF: 0.112 AC: 237 AN: 2114

Alfa AF: 0.133 Hom.: 177

Bravo AF: 0.114

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.38
PhyloP100		0.37
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: rs928114; hg19: chr9-90178806;