Submissions for variant NM_001999.4(FBN2):c.7145G>A (p.Arg2382Gln)

gnomAD frequency: 0.00001  dbSNP: rs757161476

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198313	SCV000250311	uncertain significance	not provided	2014-01-18	criteria provided, single submitter	clinical testing	p.Arg2382Gln (R2382Q) CGA>CAA: c.7145 G>A in exon 57 of the FBN2 gene (NM_001999.3) The R2382Q variant in the FBN2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The R2382Q variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The R2382 residue is conserved across species. In silico analysis predicts R2382Q is damaging to the protein structure/function. The R2382Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no disease-causing mutations in nearby residues have been reported, suggesting this region of the protein may be tolerant of change. This variant was found in TAAD,FBN2.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000656228	SCV000747833	uncertain significance	Congenital contractural arachnodactyly	2018-01-12	no assertion criteria provided	clinical testing	The observed variant c.7145G>A (p.R2382Q) is not reported in 1000 Genomes and has a minor allele frequency of 0.000008767 in ExAC databases. The in silico prediction of the variant is disease causing by MutationTaster2, tolerated by SIFT, and possibly damaging by PolyPhen2.