NM_001330071.2:c.824-15739T>G

Variant names:

• chr13-35887079-A-C
• rs7990263
• NM_001330071.2:c.824-15739T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.824-15739T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,052 control chromosomes in the GnomAD database, including 23,945 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 0.55 (23945 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-15739T>G		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.824-15739T>G		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-15739T>G		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-15739T>G		intron_variant	Intron 4 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.83-9548A>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82996 AN: 151934 Hom.: 23946 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.562

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

GnomAD4 genome AF: 0.546 AC: 83003 AN: 152052 Hom.: 23945 Cov.: 33 AF XY: 0.540 AC XY: 40144 AN XY: 74326

African (AFR) AF: 0.345 AC: 14324 AN: 41482

American (AMR) AF: 0.540 AC: 8256 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2312 AN: 3472

East Asian (EAS) AF: 0.449 AC: 2309 AN: 5148

South Asian (SAS) AF: 0.459 AC: 2211 AN: 4814

European-Finnish (FIN) AF: 0.622 AC: 6569 AN: 10568

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45078 AN: 67978

Other (OTH) AF: 0.559 AC: 1179 AN: 2110

Alfa AF: 0.623 Hom.: 51111

Bravo AF: 0.534

Asia WGS AF: 0.402 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-1.1
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: rs7990263; hg19: chr13-36461216;