chr13-35819238-A-G

Variant names:

• chr13-35819238-A-G
• rs1926467
• NM_001330071.2:c.1554+3491T>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.1554+3491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 151,928 control chromosomes in the GnomAD database, including 30,525 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 0.61 (30525 hom., cov: 31)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.855 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.1554+3491T>C		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.1554+3491T>C		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.1554+3491T>C		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.1554+3491T>C		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.1554+3491T>C		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.1554+3491T>C		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92776 AN: 151810 Hom.: 30477 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.611 AC: 92878 AN: 151928 Hom.: 30525 Cov.: 31 AF XY: 0.605 AC XY: 44921 AN XY: 74264

African (AFR) AF: 0.862 AC: 35749 AN: 41470

American (AMR) AF: 0.592 AC: 9037 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2004 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3746 AN: 5146

South Asian (SAS) AF: 0.476 AC: 2290 AN: 4814

European-Finnish (FIN) AF: 0.404 AC: 4256 AN: 10544

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33945 AN: 67918

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.539 Hom.: 12650

Bravo AF: 0.642

Asia WGS AF: 0.606 AC: 2110 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	0.97
DANN	Benign	0.48
PhyloP100		-0.75
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: rs1926467; hg19: chr13-36393375; COSMIC: COSV55206957;