ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.8674G>T (p.Asp2892Tyr) (rs557212203)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195458 SCV000250261 uncertain significance not specified 2013-11-01 criteria provided, single submitter clinical testing p.Asp2892Tyr (GAT>TAT): c.8674 G>T in exon 65 of the FBN2 gene (NM_001999.3) The Asp2892Tyr variant in the FBN2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Asp2892Tyr results in a non-conservative amino acid substitution of a negatively charged Aspartic acid residue with a neutral, polar Tyrosine residue at a position that is not conserved across species. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. The Asp2892Tyr 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 mutations affecting nearby residues have been reported in association with contractural arachnodactyly, suggesting 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 Asp2892Tyr is a disease-causing mutation or a rare benign variant.This variant was found in TAAD
Invitae RCV000541423 SCV000630268 benign Congenital contractural arachnodactyly 2020-10-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000541423 SCV001313730 benign Congenital contractural arachnodactyly 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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