Submissions for variant NM_001999.4(FBN2):c.4647C>T (p.Asn1549=)

gnomAD frequency: 0.00076  dbSNP: rs146662880

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125054	SCV000168494	benign	not specified	2013-02-26	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205287	SCV000261854	benign	Congenital contractural arachnodactyly	2025-01-29	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000125054	SCV000270204	likely benign	not specified	2015-07-14	criteria provided, single submitter	clinical testing	p.Asn1549Asn in exon 36 of FBN2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.1% (82/66738) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs146662880).
Ambry Genetics	RCV002310697	SCV000318882	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2015-03-06	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Illumina Laboratory Services, Illumina	RCV000205287	SCV000452590	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001579404	SCV000603691	benign	not provided	2022-10-21	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659621	SCV000781460	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277257	SCV002565927	benign	Ehlers-Danlos syndrome	2020-08-31	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000659621	SCV002566582	benign	Connective tissue disorder	2021-09-27	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498602	SCV002804927	likely benign	Congenital contractural arachnodactyly; Macular degeneration, early-onset	2022-05-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000125054	SCV004029407	benign	not specified	2023-07-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001579404	SCV004161335	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	FBN2: BP4, BS1, BS2
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579404	SCV001807115	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579404	SCV001972106	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945121	SCV004759507	likely benign	FBN2-related disorder	2019-10-28	no assertion criteria provided	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).