dbSNP rs1279022780: DCLK1:p.Ala357Ser (chr13-35839143-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330071.2(DCLK1):c.1069G>T(p.Ala357Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A357T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DCLK1
NM_001330071.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10873896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2 link	c.1069G>T	p.Ala357Ser	missense_variant	Exon 7 of 17	ENST00000360631.8	NP_001317000.1	O15075-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCLK1	ENST00000360631.8 link	c.1069G>T	p.Ala357Ser	missense_variant	Exon 7 of 17	5	NM_001330071.2	ENSP00000353846.3	O15075-1
DCLK1	ENST00000255448.8 link	c.1069G>T	p.Ala357Ser	missense_variant	Exon 7 of 18	1		ENSP00000255448.4	O15075-2
DCLK1	ENST00000379893.5 link	c.148G>T	p.Ala50Ser	missense_variant	Exon 3 of 13	2		ENSP00000369223.1	O15075-4
DCLK1	ENST00000615680.5 link	c.148G>T	p.Ala50Ser	missense_variant	Exon 3 of 14	2		ENSP00000484452.1	O15075-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714750

African (AFR)

AF:

0.00

AC:

AN:

33302

American (AMR)

AF:

0.00

AC:

AN:

41498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25714

East Asian (EAS)

AF:

0.00

AC:

AN:

39168

South Asian (SAS)

AF:

0.00

AC:

AN:

82384

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102474

Other (OTH)

AF:

0.00

AC:

AN:

59734

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.086

.;T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.51

.;N;.;N

PhyloP100

3.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.76

.;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.90

.;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.0040

B;.;B;B

Vest4

0.22

MutPred

0.20

.;Gain of phosphorylation at A357 (P = 0.0068);.;Gain of phosphorylation at A357 (P = 0.0068);

MVP

0.45

MPC

1.8

ClinPred

0.76

GERP RS

4.8

Varity_R

0.064

gMVP

0.47

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over