rs72652878

Variant names:

• chr13-35864978-G-T
• rs72652878
• NM_001330071.2:c.940+6246C>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.940+6246C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,062 control chromosomes in the GnomAD database, including 500 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 0.077 (500 hom., cov: 31)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• 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=-0.88).
• 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+6246C>A		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+6246C>A		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.940+6246C>A		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.940+6246C>A		intron_variant	Intron 5 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.82+6832G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11657 AN: 151944 Hom.: 500 Cov.: 31

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0409

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0767 AC: 11660 AN: 152062 Hom.: 500 Cov.: 31 AF XY: 0.0771 AC XY: 5729 AN XY: 74346

African (AFR) AF: 0.0350 AC: 1455 AN: 41514

American (AMR) AF: 0.0693 AC: 1059 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0414 AC: 199 AN: 4810

European-Finnish (FIN) AF: 0.133 AC: 1404 AN: 10552

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7069 AN: 67950

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0884 Hom.: 79

Bravo AF: 0.0698

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.5
DANN	Benign	0.35
PhyloP100		0.094
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: rs72652878; hg19: chr13-36439115;