rs1539549

Variant names:

• chr13-35877744-C-T
• rs1539549
• NM_001330071.2:c.824-6404G>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.824-6404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,904 control chromosomes in the GnomAD database, including 10,379 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 0.37 (10379 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 6 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]

ENSG00000306415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-6404G>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.824-6404G>A		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-6404G>A		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-6404G>A		intron_variant	Intron 4 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.83-18883C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55462 AN: 151788 Hom.: 10371 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.365 AC: 55512 AN: 151904 Hom.: 10379 Cov.: 33 AF XY: 0.371 AC XY: 27551 AN XY: 74226

African (AFR) AF: 0.419 AC: 17369 AN: 41410

American (AMR) AF: 0.428 AC: 6533 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3472

East Asian (EAS) AF: 0.404 AC: 2080 AN: 5146

South Asian (SAS) AF: 0.396 AC: 1907 AN: 4810

European-Finnish (FIN) AF: 0.347 AC: 3659 AN: 10534

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21306 AN: 67940

Other (OTH) AF: 0.348 AC: 734 AN: 2110

Alfa AF: 0.339 Hom.: 23818

Bravo AF: 0.376

Asia WGS AF: 0.389 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		0.74
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: rs1539549; hg19: chr13-36451881;