rs10507435

Variant names:

• chr13-35866859-A-G
• rs10507435
• NM_001330071.2:c.940+4365T>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+4365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,134 control chromosomes in the GnomAD database, including 5,358 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 (5358 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• 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]

ENSG00000306415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.940+4365T>C		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+4365T>C		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.940+4365T>C		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.940+4365T>C		intron_variant	Intron 5 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.82+8713A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39993 AN: 152016 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.263 AC: 40042 AN: 152134 Hom.: 5358 Cov.: 32 AF XY: 0.264 AC XY: 19674 AN XY: 74386

African (AFR) AF: 0.271 AC: 11249 AN: 41494

American (AMR) AF: 0.342 AC: 5226 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5182

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2757 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16846 AN: 67976

Other (OTH) AF: 0.251 AC: 531 AN: 2112

Alfa AF: 0.253 Hom.: 2633

Bravo AF: 0.271

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.30
PhyloP100		0.48
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: rs10507435; hg19: chr13-36440996;