ClinVar Miner

Submissions for variant NM_000206.3(IL2RG):c.294del (p.Val99fs)

dbSNP: rs2092261618
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001063995 SCV001228867 pathogenic X-linked severe combined immunodeficiency 2019-03-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in IL2RG are known to be pathogenic (PMID: 9058718, 10794430). This variant has not been reported in the literature in individuals with IL2RG-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val99Serfs*48) in the IL2RG gene. It is expected to result in an absent or disrupted protein product.
Lifecell International Pvt. Ltd RCV001063995 SCV003925473 pathogenic X-linked severe combined immunodeficiency criteria provided, single submitter clinical testing A Hemizygote Frameshift variant c.294delA in Exon 3 of the IL2RG gene that results in the amino acid substitution p.Val99fs*48 was identified. The observed variant has a miniimum allele frequency of 00/00% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic( variant ID 858175). This variant has been observed in many individuals affected with Severe combined immunodeficiency, X-linked reported by (Niemela JE, et al., 2000). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.

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