Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155754 | SCV003844697 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2023-02-14 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exons 11-12 in the PMS2 gene. A presumed nomenclature of c.(1144+1_1145-1)_(2174+1_2175-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in a frameshift in the PMS2 gene. The variant was absent in 21694 control chromosomes in gnomAD, structural variants dataset. Exons 11-12 duplication has been reported in the literature in individuals that had multi gene panel testing done for cancer, affected with colon cancer, and suspected with Lynch Syndrome (examples: LaDuca_2014, Li_2015, Broeke_2015, Schwartz_2021). These data indicate that the variant is likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |