rs2051090

Variant names:

• chr13-35880056-G-A
• rs2051090
• NM_001330071.2:c.824-8716C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-35880056-G-A
• chr13-35880056-G-C
• chr13-35880056-G-T

Variant summary

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

The NM_001330071.2(DCLK1):​c.824-8716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,996 control chromosomes in the GnomAD database, including 16,072 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 0.46 (16072 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-8716C>T		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.824-8716C>T		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-8716C>T		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-8716C>T		intron_variant	Intron 4 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.83-16571G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69451 AN: 151878 Hom.: 16062 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.457 AC: 69497 AN: 151996 Hom.: 16072 Cov.: 32 AF XY: 0.452 AC XY: 33608 AN XY: 74272

African (AFR) AF: 0.519 AC: 21519 AN: 41460

American (AMR) AF: 0.432 AC: 6607 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1396 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1460 AN: 5156

South Asian (SAS) AF: 0.345 AC: 1657 AN: 4802

European-Finnish (FIN) AF: 0.440 AC: 4641 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30977 AN: 67966

Other (OTH) AF: 0.398 AC: 841 AN: 2112

Alfa AF: 0.450 Hom.: 69934

Bravo AF: 0.460

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.71
PhyloP100		-0.66
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: rs2051090; hg19: chr13-36454193; COSMIC: COSV55172046;