NM_001330071.2:c.941-7226C>G

Variant names:

• chr13-35861819-G-C
• rs72652882
• NM_001330071.2:c.941-7226C>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.941-7226C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 143,434 control chromosomes in the GnomAD database, including 424 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 0.066 (424 hom., cov: 30)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.941-7226C>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.941-7226C>G		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.941-7226C>G		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.941-7226C>G		intron_variant	Intron 5 of 6	5		ENSP00000369222.4
ENSG00000306415	ENST00000818218.1	n.82+3673G>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9411 AN: 143320 Hom.: 423 Cov.: 30

Gnomad AFR AF: 0.0147

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00643

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0655 AC: 9402 AN: 143434 Hom.: 424 Cov.: 30 AF XY: 0.0672 AC XY: 4715 AN XY: 70210

African (AFR) AF: 0.0147 AC: 591 AN: 40258

American (AMR) AF: 0.0597 AC: 845 AN: 14146

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 572 AN: 3314

East Asian (EAS) AF: 0.00644 AC: 33 AN: 5122

South Asian (SAS) AF: 0.0699 AC: 330 AN: 4724

European-Finnish (FIN) AF: 0.122 AC: 1225 AN: 10068

Middle Eastern (MID) AF: 0.116 AC: 30 AN: 258

European-Non Finnish (NFE) AF: 0.0881 AC: 5525 AN: 62734

Other (OTH) AF: 0.0786 AC: 153 AN: 1946

Alfa AF: 0.0687 Hom.: 61

Bravo AF: 0.0560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.47
PhyloP100		0.66
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: rs72652882; hg19: chr13-36435956;