Submissions for variant NM_002185.5(IL7R):c.898_902del (p.Pro300fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003074929	SCV003459954	uncertain significance	Immunodeficiency 104	2022-03-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro300Lysfs*9) in the IL7R gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 160 amino acid(s) of the IL7R protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with IL7R-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the C-terminus of the IL7R protein. Other variant(s) that disrupt this region (p.Gln331Hisfs*2) have been observed in individuals with IL7R-related conditions (PMID: 26123418). This suggests that this may be a clinically significant region of the protein. 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.