NM_001330071.2:c.824-6592T>C

Variant names:

• chr13-35877932-A-G
• rs1750921
• NM_001330071.2:c.824-6592T>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.824-6592T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,110 control chromosomes in the GnomAD database, including 38,060 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 0.70 (38060 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-6592T>C		intron_variant	Intron 4 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.824-6592T>C		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-6592T>C		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-6592T>C		intron_variant	Intron 4 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.83-18695A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106710 AN: 151992 Hom.: 38050 Cov.: 33

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.702 AC: 106764 AN: 152110 Hom.: 38060 Cov.: 33 AF XY: 0.704 AC XY: 52308 AN XY: 74348

African (AFR) AF: 0.571 AC: 23704 AN: 41486

American (AMR) AF: 0.704 AC: 10768 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2916 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3431 AN: 5160

South Asian (SAS) AF: 0.757 AC: 3643 AN: 4814

European-Finnish (FIN) AF: 0.747 AC: 7908 AN: 10586

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51822 AN: 67988

Other (OTH) AF: 0.733 AC: 1546 AN: 2110

Alfa AF: 0.745 Hom.: 88370

Bravo AF: 0.692

Asia WGS AF: 0.661 AC: 2297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.40
PhyloP100		-0.39
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: rs1750921; hg19: chr13-36452069;