Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519733 | SCV000617583 | pathogenic | not provided | 2022-03-08 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); Also known as c.4333-2A>G and IVS24-2A>G; This variant is associated with the following publications: (PMID: 22155606, 22034633, 19785027, 27074763, 18800150, 32427313) |
Center for Human Genetics, |
RCV000660054 | SCV000782017 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660054 | SCV001217384 | pathogenic | Neurofibromatosis, type 1 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 31 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the loss of 3 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of neurofibromatosis type 1 (PMID: 18800150, 19785027, 23913538). This variant is also known as IVS24-2A>G. ClinVar contains an entry for this variant (Variation ID: 449427). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in exon 32 (PMID: 23913538). This variant disrupts a region of the NF1 protein in which other variant(s) (p.Leu1425Pro) have been determined to be pathogenic (PMID: 10607834, 10712197, 31730495). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Greenwood Genetic Center Diagnostic Laboratories, |
RCV000519733 | SCV002051565 | pathogenic | not provided | 2021-02-10 | criteria provided, single submitter | clinical testing | PVS1, PS4_Supporting, PM2, PM6 |
Genome- |
RCV000660054 | SCV002560041 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000519733 | SCV004222171 | likely pathogenic | not provided | 2018-10-02 | criteria provided, single submitter | clinical testing | The NF1 c.4270-2A>G variant disrupts a canonical splice-acceptor site and interferes with normal NF1 mRNA splicing. This variant has been reported in the published literature in individuals with neurofibromatosis type 1 (PMID: 19785027 (2010), 23913538 (2013), 27074763 (2016), 35885913 (2022)), and breast cancer (PMID: 32427313 (2020)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |