Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001206936 | SCV001378270 | pathogenic | Neurofibromatosis, type 1 | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 27 of the NF1 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), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 9003501, 18546366, 25325900; Invitae). ClinVar contains an entry for this variant (Variation ID: 937830). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002260688 | SCV002540305 | pathogenic | not provided | 2022-07-01 | 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 (Pros et al., 2008; Sabbagh et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Also known as IVS21-2GA>G; This variant is associated with the following publications: (PMID: 25525159, 31766501, 16199547, 10712197, 18546366, 23913538, Bahsi2020[article], 25325900, 9003501, 28924536, Kamis2021[article], 24932921) |
Genome- |
RCV001206936 | SCV002559981 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002356885 | SCV002625230 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-01-08 | criteria provided, single submitter | clinical testing | The c.3709-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 28 in the NF1 gene. This mutation has been detected in individuals with a clinical diagnosis or suspicion of neurofibromatosis type 1 (Upadhyaya M et al. Hum Genet, 1997 Jan;99:88-92; Pros E et al. Hum Mutat, 2008 Sep;29:E173-93). This alteration results in deletion of the first 10 nucleotides in exon 28 (Pros E et al. Hum Mutat, 2008 Sep;29:E173-93; Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |