13-35925460-C-T

Position:

• chr13-35925460-C-T

Variant summary

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

The NM_001330071.2(DCLK1):​c.823+21898G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,122 control chromosomes in the GnomAD database, including 33,339 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 0.66 (33339 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.823+21898G>A		intron_variant		ENST00000360631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.823+21898G>A		intron_variant		5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.823+21898G>A		intron_variant		1		A1
DCLK1	ENST00000379892.4	c.823+21898G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.658 AC: 100048 AN: 152004 Hom.: 33298 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.658 AC: 100142 AN: 152122 Hom.: 33339 Cov.: 33 AF XY: 0.664 AC XY: 49350 AN XY: 74378

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.653

Alfa AF: 0.666 Hom.: 68251

Bravo AF: 0.658

Asia WGS AF: 0.688 AC: 2393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.87

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: rs7989245; hg19: chr13-36499597;