rs1556330552
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000206.3(IL2RG):c.562C>T(p.Gln188Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q188Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000206.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RG | NM_000206.3 | c.562C>T | p.Gln188Ter | stop_gained | 4/8 | ENST00000374202.7 | |
IL2RG | XM_047442089.1 | c.562C>T | p.Gln188Ter | stop_gained | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RG | ENST00000374202.7 | c.562C>T | p.Gln188Ter | stop_gained | 4/8 | 1 | NM_000206.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
X-linked severe combined immunodeficiency Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2023 | This sequence change creates a premature translational stop signal (p.Gln188*) in the IL2RG gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with severe combined immunodeficiency (PMID: 9058718, 28747913). ClinVar contains an entry for this variant (Variation ID: 463379). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at