Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV003469593 | SCV004207876 | likely pathogenic | Lynch syndrome 4 | 2022-11-22 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001357092 | SCV001552439 | likely pathogenic | Malignant tumor of breast | no assertion criteria provided | clinical testing | The PMS2 p.Lys804* variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, COGR, Cosmic, MutDB, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.2410A>T variant leads to a premature stop codon at position 804, which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PMS2 gene are an established mechanism of disease in PMS2 associated cancers and is the type of variant expected to cause the disorder. However, this variant occurs less than 50 base pairs from the penultimate exon junction and nonsense mutations in this region may not be subjected to nonsense mediated RNA decay, although further study would be required to validate this hypothesis and it is currently not possible to determine whether or not this might influence the severity of the disorder. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |