Submissions for variant NM_022124.6(CDH23):c.9381-2A>G

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV004528739	SCV004111438	pathogenic	CDH23-related disorder	2023-04-21	criteria provided, single submitter	clinical testing	The CDH23 c.9381-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in CDH23 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics	RCV003475574	SCV004210592	likely pathogenic	Pituitary adenoma 5, multiple types	2023-10-21	criteria provided, single submitter	clinical testing
Invitae	RCV003778255	SCV004640159	likely pathogenic	not provided	2023-03-15	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with CDH23-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 66 of the CDH23 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 CDH23 are known to be pathogenic (PMID: 11138009, 21940737).