15-63930399-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014326.5(DAPK2):c.632+8G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,614,132 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (45 hom.)
• Consequence: DAPK2 NM_014326.5 splice_region, intron
• Scores: Splicing: ADA: 0.005880
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.196

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-63930399-C-A is Benign according to our data. Variant chr15-63930399-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 787680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPK2	NM_014326.5	c.632+8G>T		splice_region_variant, intron_variant		ENST00000457488.6
LOC101928988	NR_120344.1	n.543+561C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPK2	ENST00000457488.6	c.632+8G>T		splice_region_variant, intron_variant		1	NM_014326.5	P1
	ENST00000558050.1	n.543+561C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 583 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00706

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00638

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00440 AC: 1106 AN: 251468 Hom.: 7 AF XY: 0.00437 AC XY: 594 AN XY: 135902

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00762

Gnomad NFE exome AF: 0.00758

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00589 AC: 8604 AN: 1461822 Hom.: 45 Cov.: 31 AF XY: 0.00560 AC XY: 4073 AN XY: 727222

Gnomad4 AFR exome AF: 0.000866

Gnomad4 AMR exome AF: 0.00127

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00704

Gnomad4 NFE exome AF: 0.00710

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.00383 AC: 583 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.00342 AC XY: 255 AN XY: 74478

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00706

Gnomad4 NFE AF: 0.00638

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00520 Hom.: 1

Bravo AF: 0.00351

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00545

EpiControl AF: 0.00551

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	DAPK2: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	1.6
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0059
dbscSNV1_RF	Benign	0.024
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: rs200278398; hg19: chr15-64222598;