13-35783913-T-C

Variant names:

• chr13-35783913-T-C
• rs4591003
• NM_001330071.2:c.2059-9214A>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.2059-9214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,018 control chromosomes in the GnomAD database, including 29,602 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 0.59 (29602 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 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.2059-9214A>G		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.2059-9214A>G		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.2132+4299A>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.2059-9214A>G		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.2132+4299A>G		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.2059-9214A>G		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89988 AN: 151900 Hom.: 29557 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.593 AC: 90085 AN: 152018 Hom.: 29602 Cov.: 32 AF XY: 0.586 AC XY: 43514 AN XY: 74312

African (AFR) AF: 0.875 AC: 36309 AN: 41490

American (AMR) AF: 0.488 AC: 7456 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1928 AN: 3464

East Asian (EAS) AF: 0.842 AC: 4359 AN: 5174

South Asian (SAS) AF: 0.473 AC: 2280 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3840 AN: 10538

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32114 AN: 67934

Other (OTH) AF: 0.551 AC: 1166 AN: 2116

Alfa AF: 0.515 Hom.: 29746

Bravo AF: 0.618

Asia WGS AF: 0.630 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.47
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: rs4591003; hg19: chr13-36358050; COSMIC: COSV55206804; COSMIC: COSV55206804;