ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.8596G>A (p.Gly2866Ser) (rs752201545)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000784952 SCV000923496 uncertain significance Congenital contractural arachnodactyly 2019-01-01 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000784953 SCV000923497 uncertain significance Macular degeneration, early-onset 2019-01-01 criteria provided, single submitter clinical testing
Invitae RCV000784952 SCV001405952 uncertain significance Congenital contractural arachnodactyly 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 2866 of the FBN2 protein (p.Gly2866Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs752201545, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 634470). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C5). 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. 5
GeneDx RCV001552287 SCV001772951 uncertain significance not provided 2020-04-22 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Does not affect a cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-related disorders (Collod-Beroud et al., 2003; Frederic et al., 2009).; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 634470; Landrum et al., 2016)

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