NM_001330071.2:c.2059-6844G>A

Variant names:

• chr13-35781543-C-T
• rs9545332
• NM_001330071.2:c.2059-6844G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.2059-6844G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,122 control chromosomes in the GnomAD database, including 7,163 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 0.28 (7163 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70
• Publications: 3 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=-0.54).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.2059-6844G>A		intron_variant	Intron 16 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.2059-6844G>A		intron_variant	Intron 16 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.2132+6669G>A		intron_variant	Intron 17 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.1138-6844G>A		intron_variant	Intron 12 of 12	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.1211+6669G>A		intron_variant	Intron 13 of 13	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42362 AN: 152006 Hom.: 7148 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.279 AC: 42410 AN: 152122 Hom.: 7163 Cov.: 33 AF XY: 0.277 AC XY: 20625 AN XY: 74356

African (AFR) AF: 0.454 AC: 18824 AN: 41478

American (AMR) AF: 0.202 AC: 3086 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 870 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2590 AN: 5170

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1711 AN: 10578

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13292 AN: 68000

Other (OTH) AF: 0.250 AC: 529 AN: 2114

Alfa AF: 0.214 Hom.: 3350

Bravo AF: 0.291

Asia WGS AF: 0.378 AC: 1320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.49
PhyloP100		1.7
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: rs9545332; hg19: chr13-36355680; COSMIC: COSV55206795;