4-150199058-AT-CG

Variant names:

• chr4-150199058-AT-CG
• ENST00000302176.8:c.992_993delATinsCG
• DCLK2 p.Tyr331Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001040261.5(DCLK2):​c.992_993delATinsCG​(p.Tyr331Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y331C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DCLK2 NM_001040261.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040261.5. 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.961+955_961+956delATinsCG		intron	N/A	NP_001035350.2	Q8N568-1
	DCLK2	NM_001040261.5		c.992_993delATinsCG	p.Tyr331Ser	missense	N/A	NP_001035351.4	Q8N568-3
	DCLK2	NM_001410852.1		c.961+955_961+956delATinsCG		intron	N/A	NP_001397781.1	Q8N568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK2	ENST00000302176.8	TSL:1	c.992_993delATinsCG	p.Tyr331Ser	missense	N/A	ENSP00000303887.8	Q8N568-3
	DCLK2	ENST00000296550.12	TSL:1 MANE Select	c.961+955_961+956delATinsCG		intron	N/A	ENSP00000296550.7	Q8N568-1
	DCLK2	ENST00000411937.6	TSL:1	n.961+955_961+956delATinsCG		intron	N/A	ENSP00000401916.2	G5E9L9

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-151120210;