Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781755 | SCV000920052 | uncertain significance | not specified | 2018-08-23 | criteria provided, single submitter | clinical testing | Variant summary: PMS2 c.2445+9A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: One predict the variant strengthens a cryptic 5 donor site. Three predict the variant creates a 5 donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 182198 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2445+9A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV003758937 | SCV004461596 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-06-08 | criteria provided, single submitter | clinical testing |