Variant 13-35828289-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001330071.2(DCLK1):c.1248T>C(p.Tyr416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,605,488 control chromosomes in the GnomAD database, including 171,032 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 0.38 ( 12870 hom., cov: 32)

Exomes 𝑓: 0.46 ( 158162 hom. )

Consequence

DCLK1
NM_001330071.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Variant links:

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]

DCLK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP7

Synonymous conserved (PhyloP=1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2 linkuse as main transcript	c.1248T>C	p.Tyr416=	synonymous_variant	9/17	ENST00000360631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8 linkuse as main transcript	c.1248T>C	p.Tyr416=	synonymous_variant	9/17	5	NM_001330071.2	P3	O15075-1
DCLK1	ENST00000255448.8 linkuse as main transcript	c.1248T>C	p.Tyr416=	synonymous_variant	9/18	1		A1	O15075-2
DCLK1	ENST00000379893.5 linkuse as main transcript	c.327T>C	p.Tyr109=	synonymous_variant	5/13	2			O15075-4
DCLK1	ENST00000615680.5 linkuse as main transcript	c.327T>C	p.Tyr109=	synonymous_variant	5/14	2			O15075-3

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57665

AN:

151922

Hom.:

12868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.587

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.530

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.436

AC:

107950

AN:

247372

Hom.:

25183

AF XY:

0.447

AC XY:

59904

AN XY:

133942

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.532

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.459

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.485

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.461

AC:

669333

AN:

1453448

Hom.:

158162

Cov.:

AF XY:

0.463

AC XY:

335065

AN XY:

723314

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.460

Gnomad4 FIN exome

AF:

0.549

Gnomad4 NFE exome

AF:

0.474

Gnomad4 OTH exome

AF:

0.452

GnomAD4 genome

AF:

0.379

AC:

57667

AN:

152040

Hom.:

12870

Cov.:

AF XY:

0.385

AC XY:

28625

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.397

Gnomad4 ASJ

AF:

0.530

Gnomad4 EAS

AF:

0.291

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.575

Gnomad4 NFE

AF:

0.479

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.468

Hom.:

13485

Bravo

AF:

0.353

Asia WGS

AF:

0.404

AC:

1405

AN:

3476

EpiCase

AF:

0.487

EpiControl

AF:

0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.3

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over