Submissions for variant NM_001999.4(FBN2):c.7055G>C (p.Gly2352Ala)

dbSNP: rs764330020

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199305	SCV000250237	uncertain significance	not provided	2013-05-20	criteria provided, single submitter	clinical testing	p.Gly2352Ala (GGA>GCA): c.7055 G>C in exon 56 of the FBN2 gene (NM_001999.3) The Gly2352Ala variant in the FBN2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Gly2352Ala results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Gly2352Ala is damaging to the protein structure/function. The Gly2352Ala 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. Nevertheless, no mutations in nearby codons have been reported in association with congenital contractural arachnodactyly, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Gly2352Ala is a disease-causing mutation or a rare benign variant.This variant was found in TAAD
AiLife Diagnostics, AiLife Diagnostics	RCV000199305	SCV002502527	uncertain significance	not provided	2021-12-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002363006	SCV002662113	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2022-09-19	criteria provided, single submitter	clinical testing	The p.G2352A variant (also known as c.7055G>C), located in coding exon 56 of the FBN2 gene, results from a G to C substitution at nucleotide position 7055. The glycine at codon 2352 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV003525877	SCV004301752	uncertain significance	Congenital contractural arachnodactyly	2023-03-29	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 213354). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is present in population databases (rs764330020, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2352 of the FBN2 protein (p.Gly2352Ala).