rs66492553

Variant names:

• chr13-35856269-C-T
• rs66492553
• NM_001330071.2:c.941-1676G>A

Variant summary

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

The NM_001330071.2(DCLK1):​c.941-1676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,032 control chromosomes in the GnomAD database, including 4,556 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 0.24 (4556 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 1 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]

ENSG00000298745 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.941-1676G>A		intron_variant	Intron 5 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.941-1676G>A		intron_variant	Intron 5 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.941-1676G>A		intron_variant	Intron 5 of 17	1		ENSP00000255448.4
ENSG00000298745	ENST00000757715.1	n.327C>T		non_coding_transcript_exon_variant	Exon 2 of 2
DCLK1	ENST00000379892.4	c.941-1676G>A		intron_variant	Intron 5 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36157 AN: 151912 Hom.: 4555 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.238 AC: 36175 AN: 152032 Hom.: 4556 Cov.: 32 AF XY: 0.238 AC XY: 17713 AN XY: 74308

African (AFR) AF: 0.300 AC: 12426 AN: 41452

American (AMR) AF: 0.229 AC: 3502 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2133 AN: 5156

South Asian (SAS) AF: 0.183 AC: 880 AN: 4820

European-Finnish (FIN) AF: 0.220 AC: 2322 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13448 AN: 67986

Other (OTH) AF: 0.223 AC: 471 AN: 2112

Alfa AF: 0.220 Hom.: 863

Bravo AF: 0.245

Asia WGS AF: 0.271 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.064
DANN	Benign	0.56
PhyloP100		-1.8
PromoterAI		-0.018	Neutral
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: rs66492553; hg19: chr13-36430406;