Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001385686 | SCV001585634 | pathogenic | CHARGE association | 2020-06-30 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the CHD7 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with CHARGE syndrome (PMID: 22461308, Invitae). 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic. |
Institute of Medical Genetics and Applied Genomics, |
RCV001385686 | SCV004027863 | pathogenic | CHARGE association | 2023-08-23 | criteria provided, single submitter | clinical testing | de novo variant predicted to disturb the conserved splice donor of exon 11, identified in a one year old infant girl suffering from global developmental delay, hypotonia, hearing impairment and ventricular septal defect, described formerly (PMID: 21158681, 22461308), LOF is a well described pathomechanism for CHD7 |