13-35850561-C-T

Variant names:

• chr13-35850561-C-T
• rs10507433
• ENST00000460982.1:c.*159G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460982.1(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 ENST00000460982.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460982.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	NM_001330071.2	MANE Select	c.1035+3938G>A		intron	N/A	NP_001317000.1
	DCLK1	NM_001438021.1		c.*159G>A		3_prime_UTR	Exon 7 of 7	NP_001424950.1
	DCLK1	NM_001195430.2		c.*159G>A		3_prime_UTR	Exon 3 of 3	NP_001182359.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	ENST00000460982.1	TSL:1	c.*159G>A		3_prime_UTR	Exon 3 of 3	ENSP00000516676.1
	DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.1035+3938G>A		intron	N/A	ENSP00000353846.3
	DCLK1	ENST00000255448.8	TSL:1	c.1035+3938G>A		intron	N/A	ENSP00000255448.4

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

African (AFR) AF: 0.235 AC: 5424 AN: 23082

American (AMR) AF: 0.352 AC: 3097 AN: 8796

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2116 AN: 14592

East Asian (EAS) AF: 0.332 AC: 8804 AN: 26494

South Asian (SAS) AF: 0.232 AC: 5921 AN: 25524

European-Finnish (FIN) AF: 0.164 AC: 5635 AN: 34266

Middle Eastern (MID) AF: 0.198 AC: 600 AN: 3026

European-Non Finnish (NFE) AF: 0.214 AC: 198428 AN: 929252

Other (OTH) AF: 0.214 AC: 9504 AN: 44444

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

African (AFR) AF: 0.237 AC: 9821 AN: 41474

American (AMR) AF: 0.283 AC: 4324 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4826

European-Finnish (FIN) AF: 0.155 AC: 1640 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13914 AN: 67996

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.208 Hom.: 6212

Bravo AF: 0.231

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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