Submissions for variant NM_000535.7(PMS2):c.706-1G>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002365050	SCV002661539	likely pathogenic	Hereditary cancer-predisposing syndrome	2020-09-22	criteria provided, single submitter	clinical testing	The c.706-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 7 of the PMS2 gene. Based on internal structural assessment, this alteration disrupts the structure of the ATPase domain (Guarné A et al. EMBO J. 2001 Oct;20:5521-31). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Myriad Genetics, Inc.	RCV004793795	SCV005405176	likely pathogenic	Lynch syndrome 4	2024-08-20	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.