9-87643404-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_004938.4(DAPK1):c.947A>G(p.Gln316Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 26)
• Consequence: DAPK1 NM_004938.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.77

Genes affected

DAPK1 (HGNC:2674): (death associated protein kinase 1) Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, DAPK1
• BP4: Computational evidence support a benign effect (MetaRNN=0.32972485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPK1	NM_004938.4	c.947A>G	p.Gln316Arg	missense_variant	11/26	ENST00000408954.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPK1	ENST00000408954.8	c.947A>G	p.Gln316Arg	missense_variant	11/26	2	NM_004938.4	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

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

Aug 02, 2021

The c.947A>G (p.Q316R) alteration is located in exon 11 (coding exon 10) of the DAPK1 gene. This alteration results from a A to G substitution at nucleotide position 947, causing the glutamine (Q) at amino acid position 316 to be replaced by an arginine (R). 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	0.79
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
Cadd	Uncertain	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.062	T;T;.;T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	L;L;L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.74	N;N;N;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.24	T;T;T;T;.;T
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.14	B;B;.;B;B;.
Vest4		0.27
MutPred		0.33		Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP		0.69
MPC		0.47
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-90258319;