rs1170994

Variant names:

• chr13-36007040-C-T
• rs1170994
• NM_001330071.2:c.724-59583G>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.724-59583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,114 control chromosomes in the GnomAD database, including 7,454 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 0.27 (7454 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.724-59583G>A		intron_variant	Intron 3 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.724-59583G>A		intron_variant	Intron 3 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.724-59583G>A		intron_variant	Intron 3 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.724-59583G>A		intron_variant	Intron 3 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41590 AN: 151996 Hom.: 7438 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.274 AC: 41643 AN: 152114 Hom.: 7454 Cov.: 33 AF XY: 0.270 AC XY: 20058 AN XY: 74360

African (AFR) AF: 0.518 AC: 21478 AN: 41460

American (AMR) AF: 0.194 AC: 2966 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.102 AC: 525 AN: 5168

South Asian (SAS) AF: 0.200 AC: 963 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2014 AN: 10578

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12078 AN: 68016

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.209 Hom.: 7351

Bravo AF: 0.284

Asia WGS AF: 0.185 AC: 644 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	2.0
DANN	Benign	0.48
PhyloP100		-0.21
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: rs1170994; hg19: chr13-36581177;