13-35870800-C-T

Variant names:

• chr13-35870800-C-T
• rs1926452
• NM_001330071.2:c.940+424G>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.940+424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,096 control chromosomes in the GnomAD database, including 2,285 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 (2285 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.940+424G>A		intron_variant	Intron 5 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.940+424G>A		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.940+424G>A		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.940+424G>A		intron_variant	Intron 5 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.82+12654C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25697 AN: 151978 Hom.: 2280 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0917

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.169 AC: 25725 AN: 152096 Hom.: 2285 Cov.: 32 AF XY: 0.169 AC XY: 12581 AN XY: 74374

African (AFR) AF: 0.202 AC: 8363 AN: 41478

American (AMR) AF: 0.215 AC: 3287 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 318 AN: 3466

East Asian (EAS) AF: 0.237 AC: 1220 AN: 5158

South Asian (SAS) AF: 0.178 AC: 855 AN: 4806

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10596

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9546 AN: 67976

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.154 Hom.: 1539

Bravo AF: 0.175

Asia WGS AF: 0.231 AC: 805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.11
Mutation Taster		=99/1	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: rs1926452; hg19: chr13-36444937;