chr13-36088840-C-T

Variant names:

• chr13-36088840-C-T
• rs9546331
• NM_001330071.2:c.723+23029G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.723+23029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,040 control chromosomes in the GnomAD database, including 7,645 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 0.31 (7645 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.723+23029G>A		intron_variant	Intron 3 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.723+23029G>A		intron_variant	Intron 3 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.723+23029G>A		intron_variant	Intron 3 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.723+23029G>A		intron_variant	Intron 3 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46884 AN: 151920 Hom.: 7637 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.309 AC: 46926 AN: 152040 Hom.: 7645 Cov.: 32 AF XY: 0.307 AC XY: 22790 AN XY: 74320

African (AFR) AF: 0.387 AC: 16036 AN: 41460

American (AMR) AF: 0.306 AC: 4669 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2731 AN: 5148

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4824

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10584

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17949 AN: 67958

Other (OTH) AF: 0.299 AC: 633 AN: 2116

Alfa AF: 0.280 Hom.: 7498

Bravo AF: 0.321

Asia WGS AF: 0.413 AC: 1432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.84
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs9546331; hg19: chr13-36662977;