Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001231934 | SCV001404472 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2019-07-31 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 12 of the ENG gene. It does not directly change the encoded amino acid sequence of the ENG protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with clinical features of hereditary hemorrhagic telangiectasia (Invitae). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the c.1686+5 nucleotide in the ENG gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 18673552). 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. |
| Gene |
RCV004778017 | SCV005389951 | uncertain significance | not provided | 2024-04-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge |