Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000213456 | SCV000279709 | uncertain significance | not provided | 2017-08-15 | criteria provided, single submitter | clinical testing | The c.1724-2 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1724-2 A>G 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.This variant is predicted to destroy the canonical splice acceptor site in intron 12 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. In addition, while other splice site variants in the FBN2 gene have been reported in the Human Gene Mutation Database in association with CCA (Stenson et al., 2014), the majority of FBN2 variants in HGMD are missense variants, suggesting haploinsufficiency may not be the primary mechanism for disease in this gene. |
Invitae | RCV003525883 | SCV004247613 | uncertain significance | Congenital contractural arachnodactyly | 2023-06-06 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 234704). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 12 of the FBN2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in FBN2 cause disease. |