rs11947645

chr4-150180520-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4161 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK2	NM_001040260.4	c.757-12618G>A		intron_variant		ENST00000296550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK2	ENST00000296550.12	c.757-12618G>A		intron_variant		1	NM_001040260.4	P4

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

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0193

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0246 Hom.: 13

Bravo AF: 0.0288

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.4
Dann	Benign	0.52

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: rs11947645; hg19: chr4-151101672;