Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003509079 | SCV004298982 | pathogenic | X-linked lymphoproliferative disease due to SH2D1A deficiency | 2023-02-21 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individuals with clinical features of SH2D1A-related conditions (PMID: 20632414; Invitae). This sequence change affects a donor splice site in intron 2 of the SH2D1A gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant is also known as Intron 2: G(+1)‚ÜíA, or g.19528G>A. Studies have shown that disruption of this splice site results in skipping of exon 2 and introduces a premature termination codon (PMID: 10598819). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |