Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002137729 | SCV002419821 | likely benign | Familial hemophagocytic lymphohistiocytosis 5 | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003388097 | SCV004099996 | likely benign | not specified | 2023-09-19 | criteria provided, single submitter | clinical testing | Variant summary: STXBP2 c.1357-13G>A alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.8e-05 in 206418 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in STXBP2 causing Familial Hemophagocytic Lymphohistiocytosis (5.8e-05 vs 0.0022), allowing no conclusion about variant significance. c.1357-13G>A has been reported in the literature in at least one individual with Secondary Hemophagocytic Lymphohistiocytosis (e.g., Eloseily_2020). This report does not allow conclusions about association of the variant with Familial Hemophagocytic Lymphohistiocytosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 31513353). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |