Description
The PMS2 p.Arg315* variant was identified in 5 of 2648 proband chromosomes (frequency: 0.002) from individuals or families with Lynch syndrome (Borras 2013, Goldberg 2015, Goodenberger 2016, Sugano 2016, Vaughn 2010). The variant was also identified in dbSNP (ID: rs200640585) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, Ambry Genetics, GeneDx and four other submitters). The variant was identified in control databases in 6 of 277038 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 1 of 24022 chromosomes (freq: 0.00004), European in 3 of 126694 chromosomes (freq: 0.00002), Ashkenazi Jewish in 1 of 10150 chromosomes (freq: 0.0001), and East Asian in 1 of 18866 chromosomes (freq: 0.00005); it was not observed in the Other, Latino, Finnish, or South Asian populations. The p.Arg315* variant leads to a premature stop codon at position 315, 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 Lynch syndrome and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | 1 | not provided | not provided | not provided |
