Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216181 | SCV000274177 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-03-02 | criteria provided, single submitter | clinical testing | The c.1539-5T>G intronic variant results from a T to G substitution 5 nucleotides upstream from coding exon 11 in the FLCN gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.05% (greater than 1900 alleles tested) in our clinical cohort. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration predicts a weakening in the native splice acceptor site efficiency; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.1539-5T>G remains unclear. |