Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000223224 | SCV000279766 | uncertain significance | not provided | 2016-01-06 | criteria provided, single submitter | clinical testing | The E2898X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This 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. The E2898X variant is predicted to cause loss of normal protein function by protein truncation, resulting the the loss of the last fifteen amino acid residues. However, only one nonsense variant in the FBN2 gene has been reported in HGMD in association with contractural arachnodactyly (Stenson et al., 2014). Most of the pathogenic variants reported in FBN2 result in missense substitutions or in-frame exon deletions/duplication (Stenson et al., 2009), which may suggest a gain-of-function effect. Therefore, loss-of-function may not be a mechanism of disease for FBN2. Based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |