rs1171092

Variant names:

• chr13-35935591-T-C
• rs1171092
• NM_001330071.2:c.823+11767A>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+11767A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 151,998 control chromosomes in the GnomAD database, including 43,155 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 (43155 hom., cov: 31)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• 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]

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 (AMR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330071.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	NM_001330071.2	MANE Select	c.823+11767A>G		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.823+11767A>G		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.823+11767A>G		intron	N/A	NP_004725.1	O15075-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.823+11767A>G		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.823+11767A>G		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.823+11767A>G		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114239 AN: 151880 Hom.: 43116 Cov.: 31

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.752 AC: 114327 AN: 151998 Hom.: 43155 Cov.: 31 AF XY: 0.754 AC XY: 56053 AN XY: 74312

African (AFR) AF: 0.765 AC: 31704 AN: 41438

American (AMR) AF: 0.817 AC: 12492 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.756 AC: 3899 AN: 5154

South Asian (SAS) AF: 0.760 AC: 3651 AN: 4806

European-Finnish (FIN) AF: 0.774 AC: 8185 AN: 10572

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

European-Non Finnish (NFE) AF: 0.730 AC: 49643 AN: 67960

Other (OTH) AF: 0.737 AC: 1557 AN: 2112

Alfa AF: 0.738 Hom.: 22368

Bravo AF: 0.757

Asia WGS AF: 0.785 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.21
DANN	Benign	0.80
PhyloP100		-0.99
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: rs1171092; hg19: chr13-36509728;