rs12430800

Positions:

• chr13-35785837-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330071.2(DCLK1):​c.2058+7529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,132 control chromosomes in the GnomAD database, including 2,159 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 0.15 (2159 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.2058+7529G>A		intron_variant		ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.2058+7529G>A		intron_variant		5	NM_001330071.2	ENSP00000353846	P3
DCLK1	ENST00000255448.8	c.2132+2375G>A		intron_variant		1		ENSP00000255448	A1
DCLK1	ENST00000379893.5	c.1137+7529G>A		intron_variant		2		ENSP00000369223
DCLK1	ENST00000615680.5	c.1211+2375G>A		intron_variant		2		ENSP00000484452

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22993 AN: 152014 Hom.: 2161 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.151 AC: 23000 AN: 152132 Hom.: 2159 Cov.: 32 AF XY: 0.153 AC XY: 11384 AN XY: 74362

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.166

Alfa AF: 0.171 Hom.: 4266

Bravo AF: 0.152

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.020
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs12430800; hg19: chr13-36359974;