chr13-35850561-C-T

Position:

• chr13-35850561-C-T

Variant summary

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

The NM_001195430.2(DCLK1):​c.*159G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,261,564 control chromosomes in the GnomAD database, including 30,104 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 0.22 (3788 hom., cov: 32)
  • Exomes 𝑓: 0.22 (26316 hom.)
• Consequence: DCLK1 NM_001195430.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1035+3938G>A		intron_variant		ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1035+3938G>A		intron_variant		5	NM_001330071.2	ENSP00000353846.3

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33259 AN: 151970 Hom.: 3771 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.215

GnomAD4 exome AF: 0.216 AC: 239529 AN: 1109476 Hom.: 26316 Cov.: 33 AF XY: 0.215 AC XY: 113474 AN XY: 526872

Gnomad4 AFR exome AF: 0.235

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.219 AC: 33308 AN: 152088 Hom.: 3788 Cov.: 32 AF XY: 0.216 AC XY: 16089 AN XY: 74342

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.212

Alfa AF: 0.205 Hom.: 4512

Bravo AF: 0.231

Asia WGS AF: 0.210 AC: 729 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	1.1
DANN	Benign	0.41

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: rs10507433; hg19: chr13-36424698; COSMIC: COSV55207174;