rs12874830

Variant names:

• chr13-35997903-A-G
• rs12874830
• NM_001330071.2:c.724-50446T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-35997903-A-G
• chr13-35997903-A-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.724-50446T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,140 control chromosomes in the GnomAD database, including 2,130 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 (2130 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 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.724-50446T>C		intron	N/A	NP_001317000.1
	DCLK1	NM_001330072.2		c.724-50446T>C		intron	N/A	NP_001317001.1
	DCLK1	NM_004734.5		c.724-50446T>C		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.724-50446T>C		intron	N/A	ENSP00000353846.3
	DCLK1	ENST00000255448.8	TSL:1	c.724-50446T>C		intron	N/A	ENSP00000255448.4
	DCLK1	ENST00000379892.4	TSL:5	c.724-50446T>C		intron	N/A	ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23719 AN: 152022 Hom.: 2129 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.156 AC: 23717 AN: 152140 Hom.: 2130 Cov.: 32 AF XY: 0.154 AC XY: 11470 AN XY: 74364

African (AFR) AF: 0.0733 AC: 3042 AN: 41526

American (AMR) AF: 0.141 AC: 2146 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1183 AN: 5158

South Asian (SAS) AF: 0.135 AC: 650 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1713 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13876 AN: 67990

Other (OTH) AF: 0.164 AC: 347 AN: 2110

Alfa AF: 0.185 Hom.: 8794

Bravo AF: 0.151

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		1.4
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: rs12874830; hg19: chr13-36572040; COSMIC: COSV55207837;