chr13-36072569-G-T

Variant names:

• chr13-36072569-G-T
• rs1159388
• NM_001330071.2:c.723+39300C>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+39300C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,168 control chromosomes in the GnomAD database, including 36,730 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 0.69 (36730 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330071.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	NM_001330071.2	MANE Select	c.723+39300C>A		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.723+39300C>A		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.723+39300C>A		intron	N/A	NP_004725.1	O15075-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.723+39300C>A		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.723+39300C>A		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.723+39300C>A		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104232 AN: 152050 Hom.: 36669 Cov.: 33

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.687

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

GnomAD4 genome AF: 0.686 AC: 104349 AN: 152168 Hom.: 36730 Cov.: 33 AF XY: 0.687 AC XY: 51133 AN XY: 74384

African (AFR) AF: 0.806 AC: 33454 AN: 41526

American (AMR) AF: 0.715 AC: 10925 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3470

East Asian (EAS) AF: 0.989 AC: 5133 AN: 5188

South Asian (SAS) AF: 0.778 AC: 3758 AN: 4830

European-Finnish (FIN) AF: 0.541 AC: 5714 AN: 10558

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40965 AN: 67988

Other (OTH) AF: 0.691 AC: 1460 AN: 2112

Alfa AF: 0.632 Hom.: 51209

Bravo AF: 0.705

Asia WGS AF: 0.892 AC: 3100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.35
PhyloP100		1.0
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: rs1159388; hg19: chr13-36646706;