rs9545424

Variant names:

• chr13-35809127-G-A
• rs9545424
• NM_001330071.2:c.1689-32C>T

Variant summary

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

The NM_001330071.2(DCLK1):​c.1689-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 1,572,050 control chromosomes in the GnomAD database, including 12,821 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 (1050 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11771 hom.)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1689-32C>T		intron_variant	Intron 12 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1689-32C>T		intron_variant	Intron 12 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.1689-32C>T		intron_variant	Intron 12 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.768-32C>T		intron_variant	Intron 8 of 12	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.768-32C>T		intron_variant	Intron 8 of 13	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16623 AN: 151958 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.118

GnomAD3 exomes AF: 0.120 AC: 29224 AN: 243024 Hom.: 1997 AF XY: 0.124 AC XY: 16322 AN XY: 131434

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.0581

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.193

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.0921

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.125 AC: 177382 AN: 1419972 Hom.: 11771 Cov.: 24 AF XY: 0.125 AC XY: 88497 AN XY: 706058

Gnomad4 AFR exome AF: 0.0667

Gnomad4 AMR exome AF: 0.0622

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0924

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.109 AC: 16627 AN: 152078 Hom.: 1050 Cov.: 32 AF XY: 0.107 AC XY: 7977 AN XY: 74352

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.0938

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.119

Alfa AF: 0.130 Hom.: 2939

Bravo AF: 0.109

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9545424; hg19: chr13-36383264; COSMIC: COSV55177950; COSMIC: COSV55177950;