Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000608507 | SCV000731622 | pathogenic | Lynch syndrome | 2017-06-13 | criteria provided, single submitter | clinical testing | This PMS2 variant is a deletion encompassing exons 10 to 14. Deletions in this r egion have been well reported in the heterozygous state in individuals with Lync h syndrome (Brea-Fernandez 2014, Rosty 2016, Senter 2008, ten Broeke 2015, van d er Klift 2005, van der Klift 2010, van der Klift 2016, van Puijenbroek 2008, Vau ghn 2013), and in the compound heterozygous state in individuals with constituti onal mismatch repair deficiency syndrome (Lavoine 2015, van der Klift 2016, Vaso vcak 2012). Larger deletions spanning this region have also been identified in m ultiple cases of Lynch syndrome (Bakry 2014, Baris 2015, Borras 2013, Brea-Ferna ndez 2014, Chmara 2013, Herkert 2011, LaDuca 2014, Lavoine 2015, Lindsay 2013, N icolaides 1994, Overbeek 2007, Peron 2008, Rosty 2016, Senter 2008, Suerink 2016 , ten Broeke 2015, van der Klift 2005, van der Klift 2010, van der Klift 2016, Vaughn 2011, Vaughn 2013, Will 2007). This deletion is expected to lead to a tru ncated or absent protein, though its exact breakpoints cannot be determined due to limitations of the testing methodology. Heterozygous loss of function of the PMS2 gene is an established disease mechanism in individuals with Lynch syndrom e. In summary, this variant meets criteria to be classified as pathogenic for Ly nch syndrome in an autosomal dominant manner based on the predicted impact to th e protein and multiple occurrences in affected individuals. |