X-1198569-CTC-TTT

Variant names:

• chrX-1198569-CTC-TTT
• NM_022148.4:c.637_639delGAGinsAAA
• CRLF2 p.Glu213Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_022148.4(CRLF2):​c.637_639delGAGinsAAA​(p.Glu213Lys) variant causes a missense change involving the alteration of a non-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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CRLF2 NM_022148.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

CRLF2 (HGNC:14281): (cytokine receptor like factor 2) This gene encodes a member of the type I cytokine receptor family. The encoded protein is a receptor for thymic stromal lymphopoietin (TSLP). Together with the interleukin 7 receptor (IL7R), the encoded protein and TSLP activate STAT3, STAT5, and JAK2 pathways, which control processes such as cell proliferation and development of the hematopoietic system. Rearrangement of this gene with immunoglobulin heavy chain gene (IGH) on chromosome 14, or with P2Y purinoceptor 8 gene (P2RY8) on the same X or Y chromosomes is associated with B-progenitor acute lymphoblastic leukemia (ALL) and Down syndrome ALL. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

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

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: -0.85264 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022148.4. 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
	CRLF2	NM_022148.4	MANE Select	c.637_639delGAGinsAAA	p.Glu213Lys	missense	N/A	NP_071431.2
	CRLF2	NM_001012288.3		c.301_303delGAGinsAAA	p.Glu101Lys	missense	N/A	NP_001012288.2	Q9HC73-3
	CRLF2	NR_110830.2		n.840+230_840+232delGAGinsAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF2	ENST00000400841.8	TSL:1 MANE Select	c.637_639delGAGinsAAA	p.Glu213Lys	missense	N/A	ENSP00000383641.3	Q9HC73-1
	CRLF2	ENST00000381567.8	TSL:1	c.301_303delGAGinsAAA	p.Glu101Lys	missense	N/A	ENSP00000370979.4	Q9HC73-3
	CRLF2	ENST00000467626.6	TSL:5	n.*126+230_*126+232delGAGinsAAA		intron	N/A	ENSP00000485269.1	A0A0C4DH06

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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: chrX-1317426;