NM_001330071.2:c.2059-9214A>G

Variant names:

• chr13-35783913-T-C
• rs4591003
• NM_001330071.2:c.2059-9214A>G

Variant summary

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

The NM_001330071.2(DCLK1):​c.2059-9214A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,018 control chromosomes in the GnomAD database, including 29,602 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 0.59 (29602 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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 (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.2059-9214A>G		intron_variant	Intron 16 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.2059-9214A>G		intron_variant	Intron 16 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.2132+4299A>G		intron_variant	Intron 17 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.1138-9214A>G		intron_variant	Intron 12 of 12	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.1211+4299A>G		intron_variant	Intron 13 of 13	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89988 AN: 151900 Hom.: 29557 Cov.: 32

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.593 AC: 90085 AN: 152018 Hom.: 29602 Cov.: 32 AF XY: 0.586 AC XY: 43514 AN XY: 74312

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.551

Alfa AF: 0.492 Hom.: 17754

Bravo AF: 0.618

Asia WGS AF: 0.630 AC: 2194 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	0.40

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: rs4591003; hg19: chr13-36358050; COSMIC: COSV55206804; COSMIC: COSV55206804;