Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001903407 | SCV002173407 | uncertain significance | Immunodeficiency 104 | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 218 of the IL7R protein (p.Ser218Asn). This variant is present in population databases (rs374232919, gnomAD 0.004%). This missense change has been observed in individual(s) with severe combined immunodeficiency (PMID: 15661025). ClinVar contains an entry for this variant (Variation ID: 1404792). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IL7R protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002236186 | SCV002511641 | uncertain significance | not specified | 2024-04-04 | criteria provided, single submitter | clinical testing | Variant summary: IL7R c.653G>A (p.Ser218Asn) results in a conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250926 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.653G>A has been reported in the literature along with another missense variant (phase not specified) in at-least one individual affected with T-minus, B-plus, NK-plus Severe Combined Immunodeficiency (example, Giliani_2005, cited in Zago_2014). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 15661025, 24759676). ClinVar contains an entry for this variant (Variation ID: 1404792). Based on the evidence outlined above, the variant was classified as uncertain significance. |