Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001377899 | SCV001575349 | likely pathogenic | X-linked severe combined immunodeficiency | 2020-03-12 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 4 of the IL2RG gene. It does not directly change the encoded amino acid sequence of the IL2RG protein, but it affects a nucleotide within the consensus splice site of the intron. 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed to be hemizygous in an individual with clinical features of severe combined immunodeficiency (Invitae). This variant is not present in population databases (ExAC no frequency). |