Submissions for variant NM_144997.7(FLCN):c.246C>T (p.Cys82=)

gnomAD frequency: 0.00020  dbSNP: rs150712346

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163467	SCV000214019	likely benign	Hereditary cancer-predisposing syndrome	2015-02-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV001085160	SCV000291440	likely benign	Birt-Hogg-Dube syndrome	2024-01-30	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756169	SCV000883895	likely benign	not provided	2017-09-16	criteria provided, single submitter	clinical testing	The c.246C>T; p.Cys82Cys variant (rs150712346) does not alter the amino acid sequence of the FLCN protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site (Alamut v2.9.0). This variant has not been reported in association with any hereditary cancer syndromes in the medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.02 percent (identified on 56 out of 276,584 chromosomes). Based on these observations, the p.Cys82Cys variant is likely to be benign.
GeneDx	RCV000756169	SCV000971148	likely benign	not provided	2020-10-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756169	SCV001151235	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	FLCN: BP4, BP7
Sema4, Sema4	RCV000163467	SCV002530132	uncertain significance	Hereditary cancer-predisposing syndrome	2021-10-08	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265640	SCV002547694	benign	not specified	2022-05-12	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002265640	SCV002551374	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952823	SCV004772449	likely benign	FLCN-related condition	2019-07-17	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000756169	SCV001957299	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756169	SCV001973158	likely benign	not provided		no assertion criteria provided	clinical testing