Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| University of Washington Department of Laboratory Medicine, |
RCV000758659 | SCV000887430 | pathogenic | Lynch syndrome | 2018-05-01 | criteria provided, single submitter | clinical testing | MSH2 NM_000251.2:c.2634+2T>C has a 99.88% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 26.5 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the MSH2 locus. See Shirts et al 2018, PMID 29887214. |
| Ambry Genetics | RCV002458362 | SCV002739986 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-18 | criteria provided, single submitter | clinical testing | The c.2634+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 15 in the MSH2 gene. Other intronic alterations at this canonical splice donor site, c.2634+2T>G and c.2634+1G>A, have been detected in multiple families meeting Amsterdam or Bethesda criteria (Liu B et al. Cancer Res. 1994 Sep;54:4590-4; Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7; Bonadona V et al. JAMA 2011 Jun;305:2304-10; Ambry internal data). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |