rs758080286
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
This summary comes from the ClinGen Evidence Repository: The c.406C>T (NM_000206.3) variant in IL2RG is a missense variant predicted to cause the substitution of Arginine by Tryptophan at amino acid 136 (p.Arg136Trp).The filtering allele frequency (the upper threshold of the 95% CI of 5/57157 alleles) of the c.406C>T variant in IL2RG is 0.00003386 for African/African American chromosomes by gnomAD v4.1.0, which is lower than the ClinGen SCID VCEP threshold (<0.000124) for PM2_Supporting. However, 04 hemizygotes were observed in gnomAD; thus, PM2 was not met, and BS2 is applicable.In summary, this variant meets the criteria to be classified as Likely Benign for X-linked T-B+ severe combined immunodeficiency due to gamma chain deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BS2 (VCEP specifications version 1.0). LINK:https://erepo.genome.network/evrepo/ui/classification/CA330970071/MONDO:0010315/129
Frequency
Consequence
NM_000206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL2RG | NM_000206.3 | c.406C>T | p.Arg136Trp | missense_variant | 3/8 | ENST00000374202.7 | |
IL2RG | XM_047442089.1 | c.406C>T | p.Arg136Trp | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL2RG | ENST00000374202.7 | c.406C>T | p.Arg136Trp | missense_variant | 3/8 | 1 | NM_000206.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000894 AC: 1AN: 111807Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33983
GnomAD3 exomes AF: 0.00000545 AC: 1AN: 183488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67932
GnomAD4 exome AF: 0.0000200 AC: 22AN: 1097861Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363219
GnomAD4 genome ? AF: 0.00000894 AC: 1AN: 111807Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33983
ClinVar
Submissions by phenotype
X-linked severe combined immunodeficiency Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 11, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at