chrX-71107763-TG-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_000206.3(IL2RG):βc.1082delCβ(p.Pro361HisfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000131 in 1,149,080 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Consequence
NM_000206.3 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL2RG | ENST00000374202.7 | c.1082delC | p.Pro361HisfsTer5 | frameshift_variant | Exon 8 of 8 | 1 | NM_000206.3 | ENSP00000363318.3 | ||
ENSG00000285171 | ENST00000646505.1 | n.924+513delC | intron_variant | Intron 7 of 11 | ENSP00000496673.1 |
Frequencies
GnomAD3 genomes AF: 0.0000537 AC: 6AN: 111833Hom.: 0 Cov.: 24 AF XY: 0.0000294 AC XY: 1AN XY: 34067
GnomAD4 exome AF: 0.00000868 AC: 9AN: 1037247Hom.: 0 Cov.: 29 AF XY: 0.00000903 AC XY: 3AN XY: 332103
GnomAD4 genome AF: 0.0000537 AC: 6AN: 111833Hom.: 0 Cov.: 24 AF XY: 0.0000294 AC XY: 1AN XY: 34067
ClinVar
Submissions by phenotype
X-linked severe combined immunodeficiency Uncertain:1
This sequence change creates a premature translational stop signal (p.Pro361Hisfs*5) in the IL2RG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the IL2RG protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with IL2RG-related conditions. ClinVar contains an entry for this variant (Variation ID: 1303318). 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. -
not provided Uncertain:1
Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation as the last 9 amino acids are lost and replaced with 4 incorrect amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at