13-36112104-A-G

Variant names:

• chr13-36112104-A-G
• NM_001330071.2:c.488T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330071.2(DCLK1):​c.488T>C​(p.Val163Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCLK1 NM_001330071.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92
• Publications: 0 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: 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=0.091793984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.488T>C	p.Val163Ala	missense_variant	Exon 3 of 17	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.488T>C	p.Val163Ala	missense_variant	Exon 3 of 17	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.488T>C	p.Val163Ala	missense_variant	Exon 3 of 18	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.488T>C	p.Val163Ala	missense_variant	Exon 3 of 7	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488T>C (p.V163A) alteration is located in exon 3 (coding exon 2) of the DCLK1 gene. This alteration results from a T to C substitution at nucleotide position 488, causing the valine (V) at amino acid position 163 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.52
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N;N;.
PhyloP100		5.9
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.60	N;N;N
REVEL	Benign	0.090
Sift	Benign	0.87	T;T;T
Sift4G	Benign	0.79	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.13
MutPred		0.20		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.42
MPC		1.4
ClinPred		0.51	D
GERP RS		5.7
Varity_R		0.097
gMVP		0.72
Mutation Taster		=68/32	polymorphism

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

hg19: chr13-36686241;