rs11947645

Variant names:

• chr4-150180520-G-A
• rs11947645
• NM_001040260.4:c.757-12618G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001040260.4(DCLK2):​c.757-12618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,244 control chromosomes in the GnomAD database, including 79 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 0.027 (79 hom., cov: 32)
• Consequence: DCLK2 NM_001040260.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 5 publications found

Genes affected

DCLK2 (HGNC:19002): (doublecortin like kinase 2) 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. Mouse studies show that the DCX gene, another family member, and this gene share function in the establishment of hippocampal organization and that their absence results in a severe epileptic phenotype and lethality, as described in human patients with lissencephaly. Multiple alternatively spliced transcript variants have been identified. [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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0274 (4166/152244) while in subpopulation AFR AF = 0.0518 (2151/41522). AF 95% confidence interval is 0.05. There are 79 homozygotes in GnomAd4. There are 1937 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4166 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040260.4. 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
	DCLK2	NM_001040260.4	MANE Select	c.757-12618G>A		intron	N/A	NP_001035350.2	Q8N568-1
	DCLK2	NM_001040261.5		c.757-12618G>A		intron	N/A	NP_001035351.4	Q8N568-3
	DCLK2	NM_001410852.1		c.757-12618G>A		intron	N/A	NP_001397781.1	Q8N568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK2	ENST00000296550.12	TSL:1 MANE Select	c.757-12618G>A		intron	N/A	ENSP00000296550.7	Q8N568-1
	DCLK2	ENST00000302176.8	TSL:1	c.757-12618G>A		intron	N/A	ENSP00000303887.8	Q8N568-3
	DCLK2	ENST00000411937.6	TSL:1	n.757-12618G>A		intron	N/A	ENSP00000401916.2	G5E9L9

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4161 AN: 152126 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0193

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0274 AC: 4166 AN: 152244 Hom.: 79 Cov.: 32 AF XY: 0.0260 AC XY: 1937 AN XY: 74446

African (AFR) AF: 0.0518 AC: 2151 AN: 41522

American (AMR) AF: 0.0240 AC: 367 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0237 AC: 82 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4828

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10606

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0193 AC: 1311 AN: 68028

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0252 Hom.: 14

Bravo AF: 0.0288

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.52
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism

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: rs11947645; hg19: chr4-151101672;