rs749468

Variant names:

• chr15-63918080-C-T
• rs749468
• ENST00000612884.4:c.*4655G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000612884.4(DAPK2):​c.*4655G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,916 control chromosomes in the GnomAD database, including 20,509 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 0.51 (20506 hom., cov: 31)
  • Exomes 𝑓: 0.55 (3 hom.)
• Consequence: DAPK2 ENST00000612884.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 6 publications found

Genes affected

DAPK2 (HGNC:2675): (death associated protein kinase 2) This gene encodes a protein that belongs to the serine/threonine protein kinase family. This protein contains a N-terminal protein kinase domain followed by a conserved calmodulin-binding domain with significant similarity to that of death-associated protein kinase 1 (DAPK1), a positive regulator of programmed cell death. Overexpression of this gene was shown to induce cell apoptosis. It uses multiple polyadenylation sites. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK2	NM_014326.5	c.859-5883G>A		intron_variant	Intron 9 of 11	ENST00000457488.6	NP_055141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK2	ENST00000457488.6	c.859-5883G>A		intron_variant	Intron 9 of 11	1	NM_014326.5	ENSP00000408277.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77266 AN: 151776 Hom.: 20495 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.514

GnomAD4 exome AF: 0.545 AC: 12 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.643 AC: 9 AN: 14

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.509 AC: 77301 AN: 151894 Hom.: 20506 Cov.: 31 AF XY: 0.514 AC XY: 38133 AN XY: 74208

African (AFR) AF: 0.395 AC: 16358 AN: 41408

American (AMR) AF: 0.530 AC: 8084 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2020 AN: 3464

East Asian (EAS) AF: 0.936 AC: 4826 AN: 5156

South Asian (SAS) AF: 0.681 AC: 3277 AN: 4812

European-Finnish (FIN) AF: 0.525 AC: 5532 AN: 10538

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35456 AN: 67946

Other (OTH) AF: 0.520 AC: 1095 AN: 2106

Alfa AF: 0.512 Hom.: 4659

Bravo AF: 0.507

Asia WGS AF: 0.781 AC: 2713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		1.4
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: rs749468; hg19: chr15-64210279;