ClinVar Miner

Submissions for variant NM_144997.7(FLCN):c.250-2A>G (rs398124533)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082633 SCV000114675 pathogenic not provided 2012-08-02 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239670 SCV000298040 pathogenic Multiple fibrofolliculomas 2016-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000082633 SCV000321650 pathogenic not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted FLCN c.250-2A>G or IVS4-2A>G and consists of an A>G nucleotide substitution at the -2 position of intron 4 of the FLCN gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in multiple individuals with Birt-Hogg-Dub? syndrome (Toro 2008, Mikesell 2014). Based on the current evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000492149 SCV000580730 pathogenic Hereditary cancer-predisposing syndrome 2019-01-25 criteria provided, single submitter clinical testing Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000239670 SCV000632865 pathogenic Multiple fibrofolliculomas 2019-12-17 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the FLCN gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in in individuals and a family affected with Birt-Hogg-Dub syndrome (PMID: 18234728). This variant is also known as IVS4-2A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 96481). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000239670 SCV000023701 pathogenic Multiple fibrofolliculomas 2009-09-01 no assertion criteria provided literature only

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