ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.1539-2A>G (rs878855214)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000230210 SCV000291436 likely pathogenic Multiple fibrofolliculomas 2017-06-22 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in the last intron (intron 13) of the FLCN gene. It is expected to disrupt mRNA splicing and likely results in a disrupted protein product. This variant has been reported in the literature in individuals affected with Birt-Hogg-Dubé syndrome (PMID: 25302759, 25537564, 27652079). In summary, donor and acceptor splice site variants are typically loss-of-function (PMID: 16199547), and loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
GeneDx RCV000498117 SCV000589813 likely pathogenic not provided 2017-06-20 criteria provided, single submitter clinical testing The c.1539-2A>G splice site variant in the FLCN gene has been previously reported in at least one individual with multiple pneumothoraces and lung cysts (Johannesma et al., 2014; Johannesma et al., 2015). This variant destroys the canonical splice acceptor site in intron 13, and is expected to cause abnormal gene splicing. Given the available data, c.1539-2A>G is a strong candidate for a pathogenic variant; however, the possibility it may be a rare benign variant cannot be excluded.

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