rs928114

chr9-87563891-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DAPK1	NM_004938.4	c.63-41063C>G		intron_variant		ENST00000408954.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPK1	ENST00000408954.8	c.63-41063C>G		intron_variant		2	NM_004938.4	P1

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

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.112

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs928114; hg19: chr9-90178806;