Submissions for variant NM_006949.4(STXBP2):c.1696+1G>A

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003530961	SCV004298000	uncertain significance	Familial hemophagocytic lymphohistiocytosis 5	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 18 of the STXBP2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.001%). Disruption of this splice site has been observed in individual(s) with hemophagocytic lymphohistiocytosis (PMID: 22451424). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Variants that disrupt 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. This variant disrupts a region of the STXBP2 protein in which other variant(s) (p.Gly566Asp) have been observed in individuals with STXBP2-related conditions (PMID: 22796692, 31976148). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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.