chr13-35870496-A-C

Variant names:

• chr13-35870496-A-C
• rs17786591
• NM_001330071.2:c.940+728T>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.940+728T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,154 control chromosomes in the GnomAD database, including 4,800 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 0.25 (4800 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• 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]

ENSG00000306415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	NM_001330071.2	MANE Select	c.940+728T>G		intron	N/A	NP_001317000.1
	DCLK1	NM_001330072.2		c.940+728T>G		intron	N/A	NP_001317001.1
	DCLK1	NM_004734.5		c.940+728T>G		intron	N/A	NP_004725.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.940+728T>G		intron	N/A	ENSP00000353846.3
	DCLK1	ENST00000255448.8	TSL:1	c.940+728T>G		intron	N/A	ENSP00000255448.4
	DCLK1	ENST00000379892.4	TSL:5	c.940+728T>G		intron	N/A	ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37919 AN: 152036 Hom.: 4797 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.249 AC: 37947 AN: 152154 Hom.: 4800 Cov.: 32 AF XY: 0.251 AC XY: 18686 AN XY: 74402

African (AFR) AF: 0.223 AC: 9242 AN: 41510

American (AMR) AF: 0.334 AC: 5112 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5174

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4820

European-Finnish (FIN) AF: 0.262 AC: 2769 AN: 10586

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16858 AN: 68000

Other (OTH) AF: 0.245 AC: 517 AN: 2110

Alfa AF: 0.248 Hom.: 1768

Bravo AF: 0.255

Asia WGS AF: 0.273 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		2.7
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: rs17786591; hg19: chr13-36444633;