Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002327232 | SCV001186498 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-03-14 | criteria provided, single submitter | clinical testing | The c.5749+2dupT intronic variant, results from a duplication of T two nucleotides downstream of coding exon 38 in the NF1 gene. This region is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001873381 | SCV002252518 | likely pathogenic | Neurofibromatosis, type 1 | 2023-02-21 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 38 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 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 neurofibromatosis, type 1 (Invitae). ClinVar contains an entry for this variant (Variation ID: 825936). 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. This variant disrupts the c.5749+5G nucleotide in the NF1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 17311297, 18546366; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |