rs886037632

Positions:

• chr16-27437574-CCTGCCA-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_181078.3(IL21R):​c.241_246del​(p.Cys81_His82del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL21R NM_181078.3 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.99

Genes affected

IL21R (HGNC:6006): (interleukin 21 receptor) The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2, 4, 7, 9, and 15. This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_181078.3.
• PP5: Variant 16-27437574-CCTGCCA-C is Pathogenic according to our data. Variant chr16-27437574-CCTGCCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 42199.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3	c.241_246del	p.Cys81_His82del	inframe_deletion	4/9	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.241_246del	p.Cys81_His82del	inframe_deletion	4/9	1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4	c.241_246del	p.Cys81_His82del	inframe_deletion	4/9	1		ENSP00000379103	P1
IL21R	ENST00000564089.5	c.241_246del	p.Cys81_His82del	inframe_deletion	5/10	5		ENSP00000456707	P1
IL21R	ENST00000697146.1	c.241_246del	p.Cys81_His82del	inframe_deletion, NMD_transcript_variant	3/7			ENSP00000513135

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cryptosporidiosis-chronic cholangitis-liver disease syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 11, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886037632; hg19: chr16-27448895;