Submissions for variant NM_001999.4(FBN2):c.976C>T (p.Pro326Ser)

gnomAD frequency: 0.00654  dbSNP: rs28763954

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000587728	SCV000168472	benign	not provided	2018-11-28	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 18767143, 20981092, 27884173, 27007659, 31316167)
Eurofins Ntd Llc (ga)	RCV000180226	SCV000232623	benign	not specified	2015-04-02	criteria provided, single submitter	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000180226	SCV000257911	benign	not specified	2015-06-25	criteria provided, single submitter	clinical testing
Invitae	RCV000232972	SCV000287290	benign	Congenital contractural arachnodactyly	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000180226	SCV000308664	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310690	SCV000317354	benign	Familial thoracic aortic aneurysm and aortic dissection	2014-11-13	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000232972	SCV000452644	likely benign	Congenital contractural arachnodactyly	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587728	SCV000603686	benign	not provided	2023-10-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587728	SCV000697908	benign	not provided	2017-03-29	criteria provided, single submitter	clinical testing	Variant summary: The FBN2 c.976C>T (p.Pro326Ser) variant causes a missense change involving the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. The variant of interest has been found in a large, broad control population, ExAC, in 796/121328 control chromosomes (6 homozygotes) at a frequency of 0.0065607, which is approximately 140 times the estimated maximal expected allele frequency of a pathogenic FBN2 variant (0.0000469), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000232972	SCV000743984	benign	Congenital contractural arachnodactyly	2016-07-27	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000232972	SCV000745434	likely benign	Congenital contractural arachnodactyly	2017-09-12	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659596	SCV000781435	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000232972	SCV001136968	benign	Congenital contractural arachnodactyly	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587728	SCV002563854	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FBN2: BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277246	SCV002565993	benign	Ehlers-Danlos syndrome	2022-05-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000659596	SCV002566612	benign	Connective tissue disorder	2022-01-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000232972	SCV000745938	benign	Congenital contractural arachnodactyly	2014-11-25	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000587728	SCV001799528	likely benign	not provided		no assertion criteria provided	clinical testing