rs72652875

Variant names:

• chr13-35867205-T-C
• rs72652875
• NM_001330071.2:c.940+4019A>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+4019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 152,246 control chromosomes in the GnomAD database, including 483 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 0.072 (483 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.940+4019A>G		intron_variant	Intron 5 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.940+4019A>G		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.940+4019A>G		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.940+4019A>G		intron_variant	Intron 5 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.82+9059T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10954 AN: 152128 Hom.: 483 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0719 AC: 10954 AN: 152246 Hom.: 483 Cov.: 32 AF XY: 0.0724 AC XY: 5390 AN XY: 74440

African (AFR) AF: 0.0188 AC: 781 AN: 41570

American (AMR) AF: 0.0674 AC: 1031 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0413 AC: 199 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10580

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7074 AN: 68012

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0593 Hom.: 87

Bravo AF: 0.0641

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.43
PhyloP100		-0.99
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: rs72652875; hg19: chr13-36441342;