X-71107741-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_StrongBS2
The NM_000206.3(IL2RG):c.1105A>G(p.Thr369Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,130,607 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★★). Synonymous variant affecting the same amino acid position (i.e. T369T) has been classified as Likely benign.
Frequency
Consequence
NM_000206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RG | NM_000206.3 | c.1105A>G | p.Thr369Ala | missense_variant | 8/8 | ENST00000374202.7 | |
IL2RG | XM_047442089.1 | c.*225A>G | 3_prime_UTR_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RG | ENST00000374202.7 | c.1105A>G | p.Thr369Ala | missense_variant | 8/8 | 1 | NM_000206.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000536 AC: 6AN: 111905Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34103
GnomAD3 exomes AF: 0.0000323 AC: 4AN: 123703Hom.: 0 AF XY: 0.0000515 AC XY: 2AN XY: 38807
GnomAD4 exome AF: 0.0000501 AC: 51AN: 1018702Hom.: 0 Cov.: 29 AF XY: 0.0000466 AC XY: 15AN XY: 322066
GnomAD4 genome ? AF: 0.0000536 AC: 6AN: 111905Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34103
ClinVar
Submissions by phenotype
X-linked severe combined immunodeficiency Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 11, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Uncertain significance, reviewed by expert panel | curation | ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen | Nov 14, 2023 | NM_000206.3(IL2RG):c.1105A>G (p.Thr369Ala) is a missense variant that has been reported in ClinVar, without patient information, however it has not been reported in the literature to our knowledge. It occurs at a low allele frequency in gnomAD v2.1. of 0.00002258 which is below the SCID VCEP established threshold of <0.000124, however this includes two adult hemizygotes (PM2_NotMet, BS2_Supporting). In summary, this variant is classified as uncertain significance due to insufficient information. Criteria applied: BS2_supporting (VCEP specifications version 1). - |
IL2RG-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at