Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002362089 | SCV002666678 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-16 | criteria provided, single submitter | clinical testing | The p.E411* pathogenic mutation (also known as c.1231G>T), located in coding exon 11 of the PMS2 gene, results from a G to T substitution at nucleotide position 1231. This changes the amino acid from a glutamic acid to a stop codon within coding exon 11. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Laboratory for Molecular Medicine, |
RCV004017927 | SCV004847656 | likely pathogenic | Lynch syndrome | 2019-04-02 | criteria provided, single submitter | clinical testing | The p.Glu411X variant in PMS2 has not been previously reported in individuals with Lynch syndrome but has been identified in 1/113484 European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This nonsense variant leads to a premature termination codon at position 411, which is predicted to lead to a truncated or absent protein. Loss of function of the PMS2 gene is an established disease mechanism in autosomal dominant Lynch syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP Criteria applied: PVS1, PM2. |