rs1539544

Variant names:

• chr13-35909344-C-T
• rs1539544
• NM_001330071.2:c.824-38004G>A

Variant summary

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

The NM_001330071.2(DCLK1):​c.824-38004G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,952 control chromosomes in the GnomAD database, including 8,338 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 0.32 (8338 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 0 publications found

Genes affected

DCLK1 (HGNC:2700): (doublecortin like kinase 1) This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.[provided by RefSeq, Sep 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-38004G>A		intron_variant	Intron 4 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.824-38004G>A		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-38004G>A		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-38004G>A		intron_variant	Intron 4 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48511 AN: 151836 Hom.: 8310 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.320 AC: 48590 AN: 151952 Hom.: 8338 Cov.: 32 AF XY: 0.324 AC XY: 24041 AN XY: 74252

African (AFR) AF: 0.413 AC: 17117 AN: 41436

American (AMR) AF: 0.334 AC: 5098 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 924 AN: 3466

East Asian (EAS) AF: 0.422 AC: 2165 AN: 5134

South Asian (SAS) AF: 0.456 AC: 2193 AN: 4812

European-Finnish (FIN) AF: 0.266 AC: 2812 AN: 10554

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17342 AN: 67972

Other (OTH) AF: 0.304 AC: 643 AN: 2112

Alfa AF: 0.287 Hom.: 2270

Bravo AF: 0.328

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		-0.027
Mutation Taster		=100/0	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: rs1539544; hg19: chr13-36483481;