ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.6074G>A (p.Gly2025Asp)

gnomAD frequency: 0.00001  dbSNP: rs547583705
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001241189 SCV001414190 uncertain significance Congenital contractural arachnodactyly 2020-01-31 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FBN2-related conditions. This variant is present in population databases (rs547583705, ExAC 0.01%). This sequence change replaces glycine with aspartic acid at codon 2025 of the FBN2 protein (p.Gly2025Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
Ambry Genetics RCV002357032 SCV002654723 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-10-03 criteria provided, single submitter clinical testing The p.G2025D variant (also known as c.6074G>A), located in coding exon 48 of the FBN2 gene, results from a G to A substitution at nucleotide position 6074. The glycine at codon 2025 is replaced by aspartic acid, an amino acid with similar properties, and is located in the cbEGF-like #31 domain. 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.

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