chr13-36089165-T-G

Variant names:

• chr13-36089165-T-G
• rs9315385
• NM_001330071.2:c.723+22704A>C

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+22704A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,182 control chromosomes in the GnomAD database, including 2,720 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 0.17 (2720 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 13 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.723+22704A>C		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+22704A>C		intron_variant	Intron 3 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.723+22704A>C		intron_variant	Intron 3 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.723+22704A>C		intron_variant	Intron 3 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26412 AN: 152064 Hom.: 2714 Cov.: 33

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.122

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.174 AC: 26425 AN: 152182 Hom.: 2720 Cov.: 33 AF XY: 0.175 AC XY: 13006 AN XY: 74380

African (AFR) AF: 0.0833 AC: 3462 AN: 41552

American (AMR) AF: 0.229 AC: 3511 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3470

East Asian (EAS) AF: 0.444 AC: 2285 AN: 5144

South Asian (SAS) AF: 0.127 AC: 613 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10574

Middle Eastern (MID) AF: 0.121 AC: 35 AN: 290

European-Non Finnish (NFE) AF: 0.195 AC: 13235 AN: 68008

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.192 Hom.: 12820

Bravo AF: 0.176

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.67
PhyloP100		0.019
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: rs9315385; hg19: chr13-36663302;