13-35868109-A-G

Variant names:

• chr13-35868109-A-G
• rs61949292
• NM_001330071.2:c.940+3115T>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.940+3115T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 144,562 control chromosomes in the GnomAD database, including 4,781 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 0.26 (4781 hom., cov: 27)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.63
• Publications: 1 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]

ENSG00000306415 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 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.940+3115T>C		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.940+3115T>C		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.940+3115T>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.940+3115T>C		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.940+3115T>C		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.940+3115T>C		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 37568 AN: 144488 Hom.: 4777 Cov.: 27

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.260 AC: 37595 AN: 144562 Hom.: 4781 Cov.: 27 AF XY: 0.263 AC XY: 18407 AN XY: 70032

African (AFR) AF: 0.247 AC: 9471 AN: 38410

American (AMR) AF: 0.354 AC: 5016 AN: 14160

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 642 AN: 3412

East Asian (EAS) AF: 0.256 AC: 1252 AN: 4898

South Asian (SAS) AF: 0.251 AC: 1154 AN: 4602

European-Finnish (FIN) AF: 0.282 AC: 2604 AN: 9228

Middle Eastern (MID) AF: 0.207 AC: 53 AN: 256

European-Non Finnish (NFE) AF: 0.250 AC: 16680 AN: 66702

Other (OTH) AF: 0.251 AC: 501 AN: 1998

Alfa AF: 0.235 Hom.: 559

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.072
PhyloP100		-4.6
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: rs61949292; hg19: chr13-36442246;