rs6563210

Variant names:

• chr13-35902310-A-G
• rs6563210
• NM_001330071.2:c.824-30970T>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.824-30970T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,106 control chromosomes in the GnomAD database, including 8,350 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 0.31 (8350 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.859
• Publications: 9 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]

LOC105370163 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-30970T>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.824-30970T>C		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-30970T>C		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-30970T>C		intron_variant	Intron 4 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47815 AN: 151988 Hom.: 8319 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.315 AC: 47897 AN: 152106 Hom.: 8350 Cov.: 32 AF XY: 0.319 AC XY: 23708 AN XY: 74356

African (AFR) AF: 0.443 AC: 18386 AN: 41482

American (AMR) AF: 0.326 AC: 4993 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3468

East Asian (EAS) AF: 0.421 AC: 2166 AN: 5144

South Asian (SAS) AF: 0.403 AC: 1942 AN: 4822

European-Finnish (FIN) AF: 0.252 AC: 2674 AN: 10602

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15982 AN: 67974

Other (OTH) AF: 0.302 AC: 639 AN: 2116

Alfa AF: 0.273 Hom.: 11960

Bravo AF: 0.327

Asia WGS AF: 0.402 AC: 1398 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.46
PhyloP100		-0.86
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: rs6563210; hg19: chr13-36476447;