Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076904 | SCV000108402 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | In-frame large deletion interrupting ATPase domain [pmid:11574484 Guarne:2001] |
| Ambry Genetics | RCV002381389 | SCV002691276 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-09 | criteria provided, single submitter | clinical testing | The c.989-296_1144+706del1158 gross deletion spans coding exon 10 of the PMS2 gene. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay. The exact functional effect of the missing amino acids is unknown; however, gross deletions are typically deleterious in nature. This gross deletion has been reported as a founder mutation in the Caucasian population and has been identified in numerous hereditary non-polyposis colon cancer (HNPCC)/Lynch syndrome patients, many of whom had tumors with isolated loss of PMS2 on immunohistochemistry (IHC) (Hendriks YM et al. Gastroenterology, 2006 Feb;130:312-22; van der Klift HM et al. Hum Mutat, 2010 May;31:578-87; Vaughn CP et al. Hum Mutat, 2010 May;31:588-93; Tomsic J et al. Clin Genet, 2013 Mar;83:238-43; Jóri B et al. Oncotarget, 2015 Dec;6:41108-22; Buchanan DD et al. J Gastroenterol Hepatol, 2017 Feb;32:427-438). A gross deletion in this region has also been reported in a Spanish Lynch syndrome family study and the proband was diagnosed with colorectal cancer at age 50 that demonstrated isolated loss of PMS2 on IHC (Brea-Fernandez AJ et al. Clin. Genet. 2014 Jun;85:583-8). In addition, a gross deletion in this region has been reported in trans with another PMS2 alteration in a French individual with clinical features of constitutional mismatch repair deficiency (CMMRD) syndrome such as café au lait spots, a glioblastoma diagnosed at age 40, and early-onset colorectal cancers diagnosed at the ages of 22, 32, 42 (Lavoine N et al. J. Med. Genet. 2015 Nov;52:770-8). As such, this alteration is interpreted as a disease-causing mutation. |
| Gene |
RCV001804829 | SCV002054091 | not provided | Lynch syndrome 1 | no assertion provided | literature only |