rs943220

chr13-35865115-G-Achr13-35865115-G-Cchr13-35865115-G-T

Variant summary

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

The NM_001330071.2(DCLK1):c.940+6109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,886 control chromosomes in the GnomAD database, including 14,490 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 (14490 hom., cov: 31)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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]

LOC105370163 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.940+6109C>T		intron_variant		ENST00000360631.8
LOC105370163	XR_941855.3	n.82+6969G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.940+6109C>T		intron_variant		5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.940+6109C>T		intron_variant		1		A1
DCLK1	ENST00000379892.4	c.940+6109C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65403 AN: 151768 Hom.: 14475 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.431 AC: 65471 AN: 151886 Hom.: 14490 Cov.: 31 AF XY: 0.430 AC XY: 31931 AN XY: 74222

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.406

Alfa AF: 0.404 Hom.: 2519

Bravo AF: 0.440

Asia WGS AF: 0.316 AC: 1102 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	0.51
Dann	Benign	0.64

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: rs943220; hg19: chr13-36439252;