ClinVar

Description

Variant summary: IL7R c.361dupA (p.Ile121AsnfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 3.6e-05 in 249940 control chromosomes (gnomAD). The variant, c.361dupA, has been reported in the literature in multiple compound heterozygous individuals affected with Severe Combined Immunodeficiency (e.g. Bayer_2014, Zago_2014, Dvorak_2017, Stray-Pedersen_2017 and Kwok_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic (n=3) or likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.