rs7327771

Variant names:

• chr13-36105375-G-A
• rs7327771
• NM_001330071.2:c.723+6494C>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.723+6494C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,004 control chromosomes in the GnomAD database, including 936 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 0.095 (936 hom., cov: 32)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330071.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	NM_001330071.2	MANE Select	c.723+6494C>T		intron	N/A	NP_001317000.1	O15075-1
	DCLK1	NM_001330072.2		c.723+6494C>T		intron	N/A	NP_001317001.1	O15075-1
	DCLK1	NM_004734.5		c.723+6494C>T		intron	N/A	NP_004725.1	O15075-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.723+6494C>T		intron	N/A	ENSP00000353846.3	O15075-1
	DCLK1	ENST00000255448.8	TSL:1	c.723+6494C>T		intron	N/A	ENSP00000255448.4	O15075-2
	DCLK1	ENST00000879266.1		c.723+6494C>T		intron	N/A	ENSP00000549325.1

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14403 AN: 151886 Hom.: 934 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0638

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0638

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0949 AC: 14429 AN: 152004 Hom.: 936 Cov.: 32 AF XY: 0.0926 AC XY: 6882 AN XY: 74310

African (AFR) AF: 0.188 AC: 7796 AN: 41428

American (AMR) AF: 0.0638 AC: 973 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 249 AN: 3468

East Asian (EAS) AF: 0.0545 AC: 282 AN: 5172

South Asian (SAS) AF: 0.0707 AC: 340 AN: 4806

European-Finnish (FIN) AF: 0.0182 AC: 193 AN: 10582

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0638 AC: 4339 AN: 67970

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.0776 Hom.: 318

Bravo AF: 0.102

Asia WGS AF: 0.0870 AC: 302 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.63
PhyloP100		0.035
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: rs7327771; hg19: chr13-36679512;