13-36073016-C-T

Variant names:

• chr13-36073016-C-T
• rs7334245
• NM_001330071.2:c.723+38853G>A

Variant summary

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

The NM_001330071.2(DCLK1):​c.723+38853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,062 control chromosomes in the GnomAD database, including 14,070 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 0.43 (14070 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813

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 = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.723+38853G>A		intron_variant	Intron 3 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.723+38853G>A		intron_variant	Intron 3 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.723+38853G>A		intron_variant	Intron 3 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.723+38853G>A		intron_variant	Intron 3 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65362 AN: 151944 Hom.: 14058 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.430 AC: 65411 AN: 152062 Hom.: 14070 Cov.: 32 AF XY: 0.425 AC XY: 31614 AN XY: 74338

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.470

Alfa AF: 0.440 Hom.: 30862

Bravo AF: 0.439

Asia WGS AF: 0.454 AC: 1576 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	0.42
DANN	Benign	0.83

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: rs7334245; hg19: chr13-36647153;