rs721936

Variant names:

• chr9-87668234-G-A
• rs721936
• NM_004938.4:c.1924-363G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-87668234-G-A
• chr9-87668234-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004938.4(DAPK1):​c.1924-363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,996 control chromosomes in the GnomAD database, including 20,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20040 hom., cov: 32)
• Consequence: DAPK1 NM_004938.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 12 publications found

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]

DAPK1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAPK1	NM_004938.4	c.1924-363G>A		intron_variant	Intron 18 of 25	ENST00000408954.8	NP_004929.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAPK1	ENST00000408954.8	c.1924-363G>A		intron_variant	Intron 18 of 25	2	NM_004938.4	ENSP00000386135.3

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73724 AN: 151880 Hom.: 19985 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.486 AC: 73840 AN: 151996 Hom.: 20040 Cov.: 32 AF XY: 0.489 AC XY: 36319 AN XY: 74302

African (AFR) AF: 0.722 AC: 29953 AN: 41464

American (AMR) AF: 0.432 AC: 6606 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 934 AN: 3464

East Asian (EAS) AF: 0.704 AC: 3628 AN: 5150

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4818

European-Finnish (FIN) AF: 0.437 AC: 4613 AN: 10552

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24949 AN: 67956

Other (OTH) AF: 0.416 AC: 879 AN: 2114

Alfa AF: 0.399 Hom.: 59361

Bravo AF: 0.501

Asia WGS AF: 0.534 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.67
PhyloP100		0.012
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs721936; hg19: chr9-90283149;