Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000571686 | SCV000670409 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-01-08 | criteria provided, single submitter | clinical testing | The c.4725-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 36 of the NF1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position.<span style="font-family:arial,sans-serif; font-size:10pt">To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 110000 alleles tested) in our clinical cohort.This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice acceptor site; however, direct evidence is unavailable.Alterations that disrupt the canonical splice acceptor site are typically deleterious in nature (ACMGRecommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007.Genet Med.2008;10:294). As such, the c.4725-1G>A variant is classified as likely pathogenic. |
Ce |
RCV001092509 | SCV001249050 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001219651 | SCV001391601 | pathogenic | Neurofibromatosis, type 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 484015). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 31533651; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 34 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). |
Genome- |
RCV001219651 | SCV002560083 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002491129 | SCV002775732 | likely pathogenic | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-10-13 | criteria provided, single submitter | clinical testing |