NM_001330071.2:c.376+4552T>C

Variant names:

• chr13-36121210-A-G
• rs9575331
• NM_001330071.2:c.376+4552T>C

Variant summary

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

The NM_001330071.2(DCLK1):​c.376+4552T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,058 control chromosomes in the GnomAD database, including 27,250 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 (27250 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.376+4552T>C		intron_variant	Intron 2 of 16	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.376+4552T>C		intron_variant	Intron 2 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.376+4552T>C		intron_variant	Intron 2 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379892.4	c.376+4552T>C		intron_variant	Intron 2 of 6	5		ENSP00000369222.4

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89931 AN: 151940 Hom.: 27206 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.592 AC: 90024 AN: 152058 Hom.: 27250 Cov.: 32 AF XY: 0.594 AC XY: 44137 AN XY: 74336

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.526

Gnomad4 OTH AF: 0.610

Alfa AF: 0.569 Hom.: 4230

Bravo AF: 0.607

Asia WGS AF: 0.785 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.85
DANN	Benign	0.49

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: rs9575331; hg19: chr13-36695347;