Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Molecular Diagnostics, |
RCV000755027 | SCV000882847 | likely pathogenic | Lynch syndrome 1 | 2018-10-24 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV004017724 | SCV004848378 | likely pathogenic | Lynch syndrome | 2020-05-13 | criteria provided, single submitter | clinical testing | The c.942+1delG variant in MSH2 has not been reported in individuals affected with Lynch syndrome and was absent from large population studies. 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 MSH2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. Other variants affecting the same splice site have been reported in ClinVar (Pathogenic or Likely Pathogenic) and c.942+1G>T has been classified as Likely pathogenic by our laboratory. In summary, although additional studies are required to establish its clinical significance, the c.942+1delG variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP criteria applied: PVS1_Strong, PM2. |