16-27430074-GC-AA
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_181078.3(IL21R):c.3_4delinsAA(p.MetPro1_?2) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
IL21R
NM_181078.3 start_lost
NM_181078.3 start_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.39
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL21R | NM_181078.3 | c.3_4delinsAA | p.MetPro1_?2 | start_lost | 2/9 | ENST00000337929.8 | NP_851564.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL21R | ENST00000337929.8 | c.3_4delinsAA | p.MetPro1_?2 | start_lost | 2/9 | 1 | NM_181078.3 | ENSP00000338010 | P1 | |
IL21R | ENST00000395754.4 | c.3_4delinsAA | p.MetPro1_?2 | start_lost | 2/9 | 1 | ENSP00000379103 | P1 | ||
IL21R | ENST00000564089.5 | c.3_4delinsAA | p.MetPro1_?2 | start_lost | 3/10 | 5 | ENSP00000456707 | P1 | ||
IL21R | ENST00000697146.1 | c.3_4delinsAA | p.MetPro1_?2 | start_lost, NMD_transcript_variant | 1/7 | ENSP00000513135 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cryptosporidiosis-chronic cholangitis-liver disease syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 18, 2018 | This sequence change affects the initiator methionine of the IL21R mRNA. The next in-frame methionine is located at codon 39. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IL21R-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the amino acids located between p.Met1 and p.Met39 is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at