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Y-1196852-A-C

Variant names:

• chrY-1196852-A-C
• rs1057519743
• ENST00000711254.1:c.695T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000711254.1(CRLF2):​c.695T>G​(p.Phe232Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: not found (cov:)
• Consequence: CRLF2 ENST00000711254.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.33

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=17.63).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF2_1	NM_022148.4_1	c.695T>G	p.Phe232Cys	missense_variant	Exon 6 of 8
CRLF2_1	NM_001012288.3_1	c.359T>G	p.Phe120Cys	missense_variant	Exon 5 of 7
CRLF2_1	XM_011545634.3	c.692T>G	p.Phe231Cys	missense_variant	Exon 6 of 8		XP_011543936.1
CRLF2_1	NR_110830.2_1	n.889T>G		non_coding_transcript_exon_variant	Exon 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF2	ENST00000711254.1	c.695T>G	p.Phe232Cys	missense_variant	Exon 6 of 8	1		ENSP00000518625.1
CRLF2	ENST00000711256.1	c.359T>G	p.Phe120Cys	missense_variant	Exon 5 of 7	1		ENSP00000518623.1
CRLF2	ENST00000711255.1	n.*175T>G		non_coding_transcript_exon_variant	Exon 6 of 8	5		ENSP00000518624.1
CRLF2	ENST00000711255.1	n.*175T>G		3_prime_UTR_variant	Exon 6 of 8	5		ENSP00000518624.1

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.

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lymphoblastic leukemia, acute, with lymphomatous features Pathogenic:1

Oct 02, 2014

Database of Curated Mutations (DoCM)

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
CADD	Benign	18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519743; hg19: chrY-1264966;