Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002021792 | SCV002315637 | likely pathogenic | X-linked lymphoproliferative disease due to SH2D1A deficiency | 2021-05-06 | criteria provided, single submitter | clinical testing | 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. 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. This variant has been observed in individual(s) with clinical features of X-linked recessive lymphoproliferative syndrome 1 (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 2 of the SH2D1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SH2D1A are known to be pathogenic (PMID: 9771704, 11049992, 15711562). |