Submissions for variant NM_001999.4(FBN2):c.5917+9T>G

gnomAD frequency: 0.00022  dbSNP: rs371439173

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000205963	SCV000261433	likely benign	Congenital contractural arachnodactyly	2023-12-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000205963	SCV000452574	likely benign	Congenital contractural arachnodactyly	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000612271	SCV000729240	benign	not specified	2017-09-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812209	SCV001471482	uncertain significance	not provided	2023-03-06	criteria provided, single submitter	clinical testing	The FBN2 c.5917+9T>G variant (rs371439173), to our knowledge, has not been reported in the medical literature but is reported in ClinVar (Variation ID: 220686). This variant is found in the general population with an allele frequency in East Asian populations of 0.06% (12/19952 alleles) in the Genome Aggregation Database. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site, although RNA studies would be required to confirm this. Due to limited information, the clinical significance of the c.5917+9T>G variant is uncertain at this time.
PreventionGenetics, part of Exact Sciences	RCV003927877	SCV004745646	likely benign	FBN2-related condition	2020-09-06	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).