Submissions for variant NM_006949.4(STXBP2):c.1356+1G>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003644799	SCV004557848	likely pathogenic	Familial hemophagocytic lymphohistiocytosis 5	2023-09-06	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 15 of the STXBP2 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 STXBP2 are known to be pathogenic (PMID: 19804848, 22451424). 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. Disruption of this splice site has been observed in individual(s) with familial hemophagocytic lymphohistiocytosis (PMID: 20823128). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Baylor Genetics	RCV003644799	SCV005052897	likely pathogenic	Familial hemophagocytic lymphohistiocytosis 5	2024-02-21	criteria provided, single submitter	clinical testing