15-63908591-C-T

Position:

• chr15-63908591-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014326.5(DAPK2):​c.1042G>A​(p.Glu348Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAPK2 NM_014326.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24617514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK2	NM_014326.5	c.1042G>A	p.Glu348Lys	missense_variant	12/12	ENST00000457488.6	NP_055141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPK2	ENST00000457488.6	c.1042G>A	p.Glu348Lys	missense_variant	12/12	1	NM_014326.5	ENSP00000408277.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445976 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.1042G>A (p.E348K) alteration is located in exon 12 (coding exon 11) of the DAPK2 gene. This alteration results from a G to A substitution at nucleotide position 1042, causing the glutamic acid (E) at amino acid position 348 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.19
Sift	Benign	0.39	T;T
Sift4G	Uncertain	0.038	D;D
Polyphen		0.63	P;P
Vest4		0.34
MutPred		0.34		Gain of ubiquitination at E348 (P = 0.0048);Gain of ubiquitination at E348 (P = 0.0048);
MVP		0.68
MPC		0.42
ClinPred		0.89	D
GERP RS		5.3
Varity_R		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-64200790;