chr13-35893178-C-G

Variant names:

• chr13-35893178-C-G
• rs1418987
• NM_001330071.2:c.824-21838G>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.824-21838G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,076 control chromosomes in the GnomAD database, including 31,185 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 0.61 (31185 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.824-21838G>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.824-21838G>C		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.824-21838G>C		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.824-21838G>C		intron_variant	Intron 4 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.83-3449C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93153 AN: 151954 Hom.: 31170 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.613 AC: 93212 AN: 152076 Hom.: 31185 Cov.: 32 AF XY: 0.619 AC XY: 46022 AN XY: 74340

African (AFR) AF: 0.323 AC: 13380 AN: 41462

American (AMR) AF: 0.758 AC: 11588 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4568 AN: 5158

South Asian (SAS) AF: 0.670 AC: 3233 AN: 4822

European-Finnish (FIN) AF: 0.694 AC: 7348 AN: 10588

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.714 AC: 48563 AN: 67974

Other (OTH) AF: 0.674 AC: 1423 AN: 2112

Alfa AF: 0.553 Hom.: 1785

Bravo AF: 0.608

Asia WGS AF: 0.756 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.70
PhyloP100		0.27
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: rs1418987; hg19: chr13-36467315;