15-63912122-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014326.5(DAPK2):c.934C>T(p.Arg312Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000043 in 1,603,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000045 ( 0 hom. )
Consequence
DAPK2
NM_014326.5 missense
NM_014326.5 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 4.39
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.809
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAPK2 | NM_014326.5 | c.934C>T | p.Arg312Cys | missense_variant | 10/12 | ENST00000457488.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAPK2 | ENST00000457488.6 | c.934C>T | p.Arg312Cys | missense_variant | 10/12 | 1 | NM_014326.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000269 AC: 4AN: 148438Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251024Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135802
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GnomAD4 exome AF: 0.0000447 AC: 65AN: 1454666Hom.: 0 Cov.: 37 AF XY: 0.0000304 AC XY: 22AN XY: 723766
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GnomAD4 genome AF: 0.0000269 AC: 4AN: 148438Hom.: 0 Cov.: 32 AF XY: 0.0000277 AC XY: 2AN XY: 72298
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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 | May 01, 2023 | The c.934C>T (p.R312C) alteration is located in exon 10 (coding exon 9) of the DAPK2 gene. This alteration results from a C to T substitution at nucleotide position 934, causing the arginine (R) at amino acid position 312 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at