rs7999483

chr13-35779300-A-Cchr13-35779300-A-T

Variant summary

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

The NM_001330071.2(DCLK1):c.2059-4601T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,140 control chromosomes in the GnomAD database, including 1,168 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 0.11 (1168 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.2059-4601T>G		intron_variant		ENST00000360631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.2059-4601T>G		intron_variant		5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.2133-4601T>G		intron_variant		1		A1
DCLK1	ENST00000379893.5	c.1138-4601T>G		intron_variant		2
DCLK1	ENST00000615680.5	c.1212-4601T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16482 AN: 152022 Hom.: 1167 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.108 AC: 16482 AN: 152140 Hom.: 1168 Cov.: 32 AF XY: 0.109 AC XY: 8098 AN XY: 74392

Gnomad4 AFR AF: 0.0680

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.117

Alfa AF: 0.110 Hom.: 1247

Bravo AF: 0.110

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.1
Dann	Benign	0.74

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: rs7999483; hg19: chr13-36353437;