Variant chr15-63971425-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_014326.5(DAPK2):c.451A>C(p.Lys151Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DAPK2
NM_014326.5 missense, splice_region

Scores

Splicing: ADA: 0.02932

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

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]

DAPK2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.961

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAPK2	NM_014326.5 linkuse as main transcript	c.451A>C	p.Lys151Gln	missense_variant, splice_region_variant	4/12	ENST00000457488.6	NP_055141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAPK2	ENST00000457488.6 linkuse as main transcript	c.451A>C	p.Lys151Gln	missense_variant, splice_region_variant	4/12	1	NM_014326.5	ENSP00000408277	P1	Q9UIK4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000403

AC:

584

AN:

1449412

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

256

AN XY:

721508

show subpopulations

Gnomad4 AFR exome

AF:

0.000241

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.000198

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000472

Gnomad4 OTH exome

AF:

0.000384

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.451A>C (p.K151Q) alteration is located in exon 4 (coding exon 3) of the DAPK2 gene. This alteration results from a A to C substitution at nucleotide position 451, causing the lysine (K) at amino acid position 151 to be replaced by a glutamine (Q). 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

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;.;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;.;.;D

M_CAP

Pathogenic

0.36

MetaRNN

Pathogenic

0.96

D;D;D;D

MetaSVM

Pathogenic

0.93

MutationAssessor

Pathogenic

4.0

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.6

D;D;.;D

REVEL

Pathogenic

0.89

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.92

MutPred

0.82

Loss of methylation at K151 (P = 0.0253);Loss of methylation at K151 (P = 0.0253);Loss of methylation at K151 (P = 0.0253);Loss of methylation at K151 (P = 0.0253);

MVP

0.97

MPC

0.73

ClinPred

1.0

GERP RS

4.3

Varity_R

0.94

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.029

dbscSNV1_RF

Benign

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over