rs10507428

Variant names:

• chr13-35802618-G-A
• rs10507428
• NM_001330071.2:c.1944+3081C>T

Variant summary

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

The NM_001330071.2(DCLK1):​c.1944+3081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,856 control chromosomes in the GnomAD database, including 2,214 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 0.15 (2214 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 2 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1944+3081C>T		intron_variant	Intron 15 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1944+3081C>T		intron_variant	Intron 15 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.1944+3081C>T		intron_variant	Intron 15 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.1023+3081C>T		intron_variant	Intron 11 of 12	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.1023+3081C>T		intron_variant	Intron 11 of 13	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23470 AN: 151738 Hom.: 2216 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.155 AC: 23479 AN: 151856 Hom.: 2214 Cov.: 32 AF XY: 0.158 AC XY: 11699 AN XY: 74182

African (AFR) AF: 0.0741 AC: 3069 AN: 41414

American (AMR) AF: 0.208 AC: 3178 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 547 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2031 AN: 5160

South Asian (SAS) AF: 0.173 AC: 835 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1663 AN: 10486

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11542 AN: 67946

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.151 Hom.: 320

Bravo AF: 0.156

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.2
DANN	Benign	0.68
PhyloP100		-0.30
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: rs10507428; hg19: chr13-36376755; COSMIC: COSV55208583; COSMIC: COSV55208583;