rs767383120
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
This summary comes from the ClinGen Evidence Repository: NM_000206.3(IL2RG):c.1076C>T is a missense variant predicted to cause substitution of Alanine by Valine at amino acid 359 (p.Ala359Val). The highest population minor allele frequency in gnomAD v4 is 0.0001453 (126/867358) in European Non-Finnish population (PM2_Supporting, BS1, and BA1 are not met). To our knowledge, this variant has not been reported in the literature in individuals affected with IL2RG related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: None (VCEP specifications version 1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA331121466/MONDO:0010315/129
Frequency
Consequence
NM_000206.3 missense
Scores
Clinical Significance
Conservation
Publications
- T-B+ severe combined immunodeficiency due to gamma chain deficiencyInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics, Myriad Women’s Health
- Omenn syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL2RG | ENST00000374202.7 | c.1076C>T | p.Ala359Val | missense_variant | Exon 8 of 8 | 1 | NM_000206.3 | ENSP00000363318.3 | ||
ENSG00000285171 | ENST00000646505.1 | n.924+507C>T | intron_variant | Intron 7 of 11 | ENSP00000496673.1 |
Frequencies
GnomAD3 genomes AF: 0.0000178 AC: 2AN: 112264Hom.: 0 Cov.: 24 show subpopulations
GnomAD2 exomes AF: 0.0000223 AC: 3AN: 134575 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.000122 AC: 127AN: 1039816Hom.: 0 Cov.: 29 AF XY: 0.000129 AC XY: 43AN XY: 332752 show subpopulations
GnomAD4 genome AF: 0.0000178 AC: 2AN: 112264Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34420 show subpopulations
ClinVar
Submissions by phenotype
X-linked severe combined immunodeficiency Uncertain:2Benign:1
- -
- -
NM_000206.3(IL2RG):c.1076C>T is a missense variant predicted to cause substitution of Alanine by Valine at amino acid 359 (p.Ala359Val). The highest population minor allele frequency in gnomAD v4 is 0.0001453 (126/867358) in European Non-Finnish population (PM2_Supporting, BS1, and BA1 are not met). To our knowledge, this variant has not been reported in the literature in individuals affected with IL2RG related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for X-linked severe combined immunodeficiency due to IL2RG deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: None (VCEP specifications version 1). -
Inborn genetic diseases Uncertain:1
The c.1076C>T (p.A359V) alteration is located in exon 8 (coding exon 8) of the IL2RG gene. This alteration results from a C to T substitution at nucleotide position 1076, causing the alanine (A) at amino acid position 359 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at