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chrY-1198571-C-T

Variant names:

• chrY-1198571-C-T
• rs200254974
• ENST00000711256.2:c.637G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2 BP4_Strong

The ENST00000711256.2(CRLF2):​c.637G>A​(p.Glu213Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov:)
• Consequence: CRLF2 ENST00000711256.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.19
• Publications: 2 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: Likely_benign. The variant received -3 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).
• BP4: Computational evidence support a benign effect (Cadd=0.829).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000711256.2. 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
	CRLF2_1	NM_022148.4_1		c.637G>A	p.Glu213Lys	missense	Exon 5 of 8
	CRLF2_1	NM_001012288.3_1		c.301G>A	p.Glu101Lys	missense	Exon 4 of 7
	CRLF2_1	NR_110830.2_1		n.840+230G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF2	ENST00000711256.2	TSL:1	c.637G>A	p.Glu213Lys	missense	Exon 5 of 8	ENSP00000518623.2
	CRLF2	ENST00000972698.1		c.301G>A	p.Glu101Lys	missense	Exon 4 of 7	ENSP00000642756.1
	CRLF2	ENST00000972739.1		n.*126+230G>A		intron	N/A	ENSP00000642781.1

Frequencies

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

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

Alfa AF: 0.000294 Hom.: 0

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
CADD	Benign	0.83
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs200254974; hg19: chrY-1267428;