ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.291-2A>G

dbSNP: rs876658584
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000222975 SCV000274030 pathogenic Hereditary cancer-predisposing syndrome 2015-02-19 criteria provided, single submitter clinical testing The c.291-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 2 in the STK11 gene. This mutation has been detected in multiple individuals meeting clinical diagnostic criteria for PJS (Westerman et al. Hum Mut 1999;13(6):476-81; Ambry internal data). In addition to this clinical data, since mutations that disrupt the canonical splice acceptor site are typically deleterious in nature, this variant is interpreted as a disease causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med 2008;10:294).
Invitae RCV000632841 SCV000754037 pathogenic Peutz-Jeghers syndrome 2023-09-06 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 of the STK11 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 STK11 are known to be pathogenic (PMID: 15188174, 16287113). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with PJS and an ampullary neuroendocrine tumor and Peutz-Jeghers syndrome (PJS) (PMID: 10408777, 23240097). This variant is also known as –2ex2 A>G. ClinVar contains an entry for this variant (Variation ID: 230469). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000632841 SCV002057359 pathogenic Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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