9-87640793-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004938.4(DAPK1):c.783-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,058 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (13 hom.)
• Consequence: DAPK1 NM_004938.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.002036
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-87640793-C-G is Benign according to our data. Variant chr9-87640793-C-G is described in ClinVar as [Benign]. Clinvar id is 783551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00537 (818/152336) while in subpopulation AFR AF= 0.0175 (727/41578). AF 95% confidence interval is 0.0164. There are 8 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 813 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAPK1	NM_004938.4	c.783-9C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000408954.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAPK1	ENST00000408954.8	c.783-9C>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_004938.4	P1

Frequencies

GnomAD3 genomes AF: 0.00534 AC: 813 AN: 152218 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00242 AC: 603 AN: 249508 Hom.: 6 AF XY: 0.00231 AC XY: 313 AN XY: 135350

Gnomad AFR exome AF: 0.0185

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000389

Gnomad SAS exome AF: 0.00693

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00108 AC: 1581 AN: 1461722 Hom.: 13 Cov.: 31 AF XY: 0.00125 AC XY: 910 AN XY: 727164

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00737

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000513

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00537 AC: 818 AN: 152336 Hom.: 8 Cov.: 33 AF XY: 0.00536 AC XY: 399 AN XY: 74488

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00169 Hom.: 2

Bravo AF: 0.00590

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.2
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.066
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: rs36211678; hg19: chr9-90255708;