Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018269 | SCV004847314 | likely pathogenic | Neurodevelopmental disorder | 2023-08-29 | criteria provided, single submitter | clinical testing | The c.3624+1G>A splice site variant in TRIP12 has not been previously reported in individuals with autosomal dominant complex neurodevelopmental disorder (also known as intellectual developmental disorder 49 and Clark-Baraitser Syndrome, OMIM: 617752). This variant was absent from large population studies (http://gnomad.broadinstitute.org). This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the TRIP12 gene is an established disease mechanism in autosomal dominant complex neurodevelopmental disorder (Bramswig 2017 PMID: 27848077, Zhang 2017 PMID: 28251352). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting. |