13-35936591-T-C

Variant names:

• chr13-35936591-T-C
• rs1171090
• NM_001330071.2:c.823+10767A>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.823+10767A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,148 control chromosomes in the GnomAD database, including 43,061 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 0.75 (43061 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.62
• Publications: 11 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.823+10767A>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.823+10767A>G		intron_variant	Intron 4 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.823+10767A>G		intron_variant	Intron 4 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.823+10767A>G		intron_variant	Intron 4 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114180 AN: 152030 Hom.: 43020 Cov.: 33

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.751 AC: 114270 AN: 152148 Hom.: 43061 Cov.: 33 AF XY: 0.753 AC XY: 56005 AN XY: 74360

African (AFR) AF: 0.761 AC: 31588 AN: 41512

American (AMR) AF: 0.816 AC: 12492 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2263 AN: 3472

East Asian (EAS) AF: 0.757 AC: 3904 AN: 5160

South Asian (SAS) AF: 0.759 AC: 3646 AN: 4806

European-Finnish (FIN) AF: 0.774 AC: 8190 AN: 10576

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.731 AC: 49700 AN: 68002

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.735 Hom.: 127719

Bravo AF: 0.755

Asia WGS AF: 0.785 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.044
DANN	Benign	0.26
PhyloP100		-3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1171090; hg19: chr13-36510728;