Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002419744 | SCV002721821 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.E677* pathogenic mutation (also known as c.2029G>T), located in coding exon 12 of the PMS2 gene, results from a G to T substitution at nucleotide position 2029. This changes the amino acid from a glutamic acid to a stop codon within coding exon 12. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Gene |
RCV002469477 | SCV002765754 | pathogenic | not provided | 2022-06-14 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Has not been previously published as pathogenic or benign to our knowledge |
Laboratory for Molecular Medicine, |
RCV004017934 | SCV004848382 | likely pathogenic | Lynch syndrome | 2020-05-13 | criteria provided, single submitter | clinical testing | The p.Glu677X variant in PMS2 has not been previously reported in individuals with Lynch syndrome and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 677, 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. |