Submissions for variant NM_000127.3(EXT1):c.1057-3C>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003227367	SCV003923814	uncertain significance	not provided	2023-05-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Multiple neighboring canonical splice variants altering the same intron 2 splice acceptor site identified in the literature (HGMD) and at GeneDx in patients with HMO; This variant is associated with the following publications: (PMID: 25525159, 23439489, 19810120)
Invitae	RCV003497982	SCV004295262	likely pathogenic	Multiple congenital exostosis	2023-02-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 2 of the EXT1 gene. It does not directly change the encoded amino acid sequence of the EXT1 protein. It affects a nucleotide within the consensus splice site. 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. Variants that disrupt 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. This variant has been observed in individual(s) with hereditary multiple osteochondroma (PMID: 19810120, 23439489; Invitae). This variant is not present in population databases (gnomAD no frequency).