ClinVar Miner

Submissions for variant NM_000206.2(IL2RG):c.202G>A (p.Glu68Lys) (rs1057520644)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427716 SCV000516730 pathogenic not provided 2015-04-15 criteria provided, single submitter clinical testing The E68K missense variant in the IL2RG gene has been reported previously in association with X-linked SCID (Markiewicz et al. 1994; Puck et al., 1997). The E68K variant was notobserved in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret E68K as a pathogenic variant.
Invitae RCV000638843 SCV000760395 likely pathogenic X-linked severe combined immunodeficiency 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 68 of the IL2RG protein (p.Glu68Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with X-linked severe combined immunodeficiency (X-SCID) and an individual affected with both West syndrome (WS) and X-SCID (PMID: 8088810, 24534054, 11129345). This variant is also known as 216G>A E68K in the literature. ClinVar contains an entry for this variant (Variation ID: 379561). Experimental studies have shown that this missense change does not bind radioactive IL-2 with high affinity (PMID: 8088810). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV001253325 SCV001428985 pathogenic Combined immunodeficiency, X-linked 2017-01-01 criteria provided, single submitter clinical testing

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