rs7999483

Variant names:

• chr13-35779300-A-C
• rs7999483
• NM_001330071.2:c.2059-4601T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-35779300-A-C
• chr13-35779300-A-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.2059-4601T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,140 control chromosomes in the GnomAD database, including 1,168 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 0.11 (1168 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.2059-4601T>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.2059-4601T>G		intron_variant	Intron 16 of 16	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.2133-4601T>G		intron_variant	Intron 17 of 17	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.1138-4601T>G		intron_variant	Intron 12 of 12	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.1212-4601T>G		intron_variant	Intron 13 of 13	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16482 AN: 152022 Hom.: 1167 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.108 AC: 16482 AN: 152140 Hom.: 1168 Cov.: 32 AF XY: 0.109 AC XY: 8098 AN XY: 74392

African (AFR) AF: 0.0680 AC: 2822 AN: 41526

American (AMR) AF: 0.107 AC: 1630 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1743 AN: 5152

South Asian (SAS) AF: 0.114 AC: 551 AN: 4818

European-Finnish (FIN) AF: 0.0892 AC: 945 AN: 10596

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7852 AN: 67982

Other (OTH) AF: 0.117 AC: 247 AN: 2116

Alfa AF: 0.109 Hom.: 1564

Bravo AF: 0.110

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.74
PhyloP100		0.13
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: rs7999483; hg19: chr13-36353437;