Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000198463 | SCV000250251 | uncertain significance | not provided | 2017-07-26 | criteria provided, single submitter | clinical testing | c.7960+5 G>A: IVS62+5 G>A in intron 62 of the FBN2 gene (NM_001999.3) The c.7960+5 G>A variant has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Other splice site mutations in the FBN2 gene have been reported in association with contractural arachnodactyly, and two splice algorithms predict that c.7960+5 G>A destroys the canonical splice donor site in intron 62. Furthermore, c.7960+5 G>A was not observed in approximately 6,500 individuals of European and African ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, without mRNA studies, the effect of c.7960+5 G>A on gene splicing, if any, remains unknown. With the clinical and molecular information available at this time, we cannot definitively determine if c.7960+5 G>A is a disease-causing mutation or a rare benign variant. This variant was found in TAAD |
Invitae | RCV003640874 | SCV004380627 | uncertain significance | Congenital contractural arachnodactyly | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 62 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. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with thoracic aortic aneurysm (Invitae). ClinVar contains an entry for this variant (Variation ID: 213367). 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 may disrupt 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. |