chr16-27437574-CCTGCCA-C

Variant names:

• chr16-27437574-CCTGCCA-C
• rs886037632
• NM_181078.3:c.241_246delTGCCAC

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_181078.3(IL21R):​c.241_246delTGCCAC​(p.Cys81_His82del) variant causes a conservative 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 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.99
• Publications: 2 publications found

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]

IL21R Gene-Disease associations (from GenCC):

• immunodeficiency disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cryptosporidiosis-chronic cholangitis-liver disease syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 42199.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181078.3. 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
	IL21R	NM_181078.3	MANE Select	c.241_246delTGCCAC	p.Cys81_His82del	conservative_inframe_deletion	Exon 4 of 9	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.307_312delTGCCAC	p.Cys103_His104del	conservative_inframe_deletion	Exon 5 of 10	NP_851565.4
	IL21R	NM_021798.4		c.241_246delTGCCAC	p.Cys81_His82del	conservative_inframe_deletion	Exon 4 of 9	NP_068570.1	Q9HBE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.241_246delTGCCAC	p.Cys81_His82del	conservative_inframe_deletion	Exon 4 of 9	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000395754.4	TSL:1	c.241_246delTGCCAC	p.Cys81_His82del	conservative_inframe_deletion	Exon 4 of 9	ENSP00000379103.4	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.241_246delTGCCAC	p.Cys81_His82del	conservative_inframe_deletion	Exon 5 of 10	ENSP00000456707.1	Q9HBE5

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

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Cryptosporidiosis-chronic cholangitis-liver disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs886037632; hg19: chr16-27448895;