Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000527112 | SCV000630261 | uncertain significance | Congenital contractural arachnodactyly | 2023-03-04 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 458779). 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 falls in intron 61 of the FBN2 gene. It does not directly change the encoded amino acid sequence of the FBN2 protein. It affects a nucleotide within the consensus splice site. 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. |
Ambry Genetics | RCV002314953 | SCV000738993 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-12-09 | criteria provided, single submitter | clinical testing | The c.7841-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 62 in the FBN2 gene. This nucleotide position is well conserved in available vertebrate species; however, T is the reference nucleotide in other vertebrate species. This alteration is predicted by ESEfinder splice site prediction tool to weaken the efficiency of the native splice acceptor site, but is not predicted to have a deleterious effect on this splice acceptor site by BDGP; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |