rs1750719

Positions:

• chr13-36041271-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.723+70598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,910 control chromosomes in the GnomAD database, including 9,565 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 0.35 (9565 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.723+70598C>A		intron_variant		ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.723+70598C>A		intron_variant		5	NM_001330071.2	ENSP00000353846	P3
DCLK1	ENST00000255448.8	c.723+70598C>A		intron_variant		1		ENSP00000255448	A1
DCLK1	ENST00000379892.4	c.723+70598C>A		intron_variant		5		ENSP00000369222

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52652 AN: 151794 Hom.: 9559 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.347 AC: 52675 AN: 151910 Hom.: 9565 Cov.: 32 AF XY: 0.343 AC XY: 25489 AN XY: 74240

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.324

Alfa AF: 0.368 Hom.: 14877

Bravo AF: 0.337

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs1750719; hg19: chr13-36615408;