rs729958

Positions:

• chr9-87672272-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.2001+3598T>C		intron_variant		ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.2001+3598T>C		intron_variant		2	NM_004938.4	ENSP00000386135	P1

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.468

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

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: rs729958; hg19: chr9-90287187;