13-35865260-T-A

Variant names:

• chr13-35865260-T-A
• rs72652877
• NM_001330071.2:c.940+5964A>T

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+5964A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,170 control chromosomes in the GnomAD database, including 2,258 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 0.16 (2258 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 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.940+5964A>T		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.940+5964A>T		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.940+5964A>T		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.940+5964A>T		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.940+5964A>T		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.940+5964A>T		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24722 AN: 152052 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.163 AC: 24755 AN: 152170 Hom.: 2258 Cov.: 32 AF XY: 0.160 AC XY: 11919 AN XY: 74386

African (AFR) AF: 0.228 AC: 9441 AN: 41490

American (AMR) AF: 0.134 AC: 2051 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 375 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4820

European-Finnish (FIN) AF: 0.158 AC: 1672 AN: 10590

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10532 AN: 68018

Other (OTH) AF: 0.154 AC: 324 AN: 2110

Alfa AF: 0.158 Hom.: 280

Bravo AF: 0.165

Asia WGS AF: 0.0440 AC: 154 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.24
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: rs72652877; hg19: chr13-36439397;