ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.134A>C (p.Asn45Thr)

dbSNP: rs1554306353
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000502451 SCV000592921 likely pathogenic Endometrial carcinoma no assertion criteria provided clinical testing The p.Asn45Thr variant has been identified in 2/18 probands (frequency: 0.056) with BMMR syndrome (T cell lympholbastic lymphoma, GI polyposis and Café-au-lait) based on both tumour and germline analysis (Bakry 2014); however, control chromosomes were not evaluated in this study, thus the prevalence of this variant in the general population could not be determined. Patient No.1 was PMS2 deficient but no IHC data was available for patient No.2 The p.Asn45Thr is the compound het variant and found with c.2186-2178delTCPMS2 in both patients. The variant was classified as pathogenic in the paper, but has not been found as pathogenic in Lynch syndrome DB. The variant was not identified in the GeneInsight, HGMD, COSMIC, Mut, MMR, InSiGHT Colon Cancer and ClinVar databases. This residue is conserved in mammals and lower organisms; however, computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainly at this time although we would lean towards a more pathogenic role of this variant. This variant is classified as predicted pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.