1-155266760-GTG-ATA

Variant names:

• chr1-155266760-GTG-ATA
• NM_001294338.2:c.805_807delCACinsTAT
• CLK2 p.His269Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001294338.2(CLK2):​c.805_807delCACinsTAT​(p.His269Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. 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. H269N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLK2 NM_001294338.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

CLK2 (HGNC:2069): (CDC like kinase 2) This gene encodes a dual specificity protein kinase that phosphorylates serine/threonine and tyrosine-containing substrates. Activity of this protein regulates serine- and arginine-rich (SR) proteins of the spliceosomal complex, thereby influencing alternative transcript splicing. Chromosomal translocations have been characterized between this locus and the PAFAH1B3 (platelet-activating factor acetylhydrolase 1b, catalytic subunit 3 (29kDa)) gene on chromosome 19, resulting in the production of a fusion protein. Note that this gene is distinct from the TELO2 gene (GeneID:9894), which shares the CLK2 alias, but encodes a protein that is involved in telomere length regulation. There is a pseudogene for this gene on chromosome 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294338.2. 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
	CLK2	NM_001294338.2	MANE Select	c.805_807delCACinsTAT	p.His269Tyr	missense	N/A	NP_001281267.1	P49760-1
	CLK2	NM_003993.4		c.802_804delCACinsTAT	p.His268Tyr	missense	N/A	NP_003984.2
	CLK2	NM_001363704.2		c.799_801delCACinsTAT	p.His267Tyr	missense	N/A	NP_001350633.1	B1AVT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLK2	ENST00000368361.9	TSL:1 MANE Select	c.805_807delCACinsTAT	p.His269Tyr	missense	N/A	ENSP00000357345.4	P49760-1
	CLK2	ENST00000361168.9	TSL:1	c.802_804delCACinsTAT	p.His268Tyr	missense	N/A	ENSP00000354856.5	P49760-3
	CLK2	ENST00000476983.5	TSL:1	n.846_848delCACinsTAT		non_coding_transcript_exon	Exon 6 of 12

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

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: chr1-155236551;