ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.780del (p.Asp261fs) (rs587779344)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076886 SCV000108382 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000076886 SCV000731683 pathogenic Lynch syndrome 2017-07-07 criteria provided, single submitter clinical testing The p.Asp261fs variant in PMS2 has been identified as a germline variant in 1 in dividual with Lynch syndrome (with PMS2-negative colorectal cancer; Borras 2013) and was absent from large population studies. This variant is predicted to caus e a frameshift, which alters the protein?s amino acid sequence beginning at posi tion 261 and leads to a premature termination codon 46 amino acids downstream. T his alteration is then predicted to lead to a truncated or absent protein. Heter ozygous loss of function of the PMS2 gene is an established disease mechanism fo r Lynch syndrome. Additionally, this variant was classified as Pathogenic on Sep tember 5, 2013 by the ClinGen-approved InSiGHT expert panel (ClinVar SCV00010838 2.2). In summary, the p.Asp261fs variant meets criteria to be classified as path ogenic for Lynch syndrome in an autosomal dominant manner.

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