13-35868109-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105370163 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.940+3115T>C		intron_variant		ENST00000360631.8
LOC105370163	XR_941855.3	n.82+9963A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.940+3115T>C		intron_variant		5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.940+3115T>C		intron_variant		1		A1
DCLK1	ENST00000379892.4	c.940+3115T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.251

Alfa AF: 0.235 Hom.: 531

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.17
Dann	Benign	0.072

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

Publications

LitVar

Other links and lift over

dbSNP: rs61949292; hg19: chr13-36442246;