Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001043668 | SCV001207426 | pathogenic | Cornelia de Lange syndrome 1 | 2019-02-14 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 2 of the NIPBL 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). Disruption of this splice site has been observed in several individuals affected with Cornelia de Lange syndrome (PMID: 15591270, 25574841, 22581668, 26701315). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837). For these reasons, this variant has been classified as Pathogenic. |