ClinVar Miner

Submissions for variant NM_006949.4(STXBP2):c.169+2T>G

dbSNP: rs1555768979
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523271 SCV000619905 pathogenic not provided 2017-08-08 criteria provided, single submitter clinical testing The c.169+2T>G variant in the STXBP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.169+2T>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.169+2T>G as a pathogenic variant.
Baylor Genetics RCV003464116 SCV004205627 likely pathogenic Familial hemophagocytic lymphohistiocytosis 5 2023-09-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003464116 SCV004677324 likely pathogenic Familial hemophagocytic lymphohistiocytosis 5 2023-06-30 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with STXBP2-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 451232). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 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).

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