ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1743del (p.Glu582fs) (rs1057517801)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412980 SCV000490731 pathogenic not provided 2015-08-03 criteria provided, single submitter clinical testing The c.1743delA variant in the PMS2 gene has not been published previously as a pathogenic variant, to our knowledge. However, other frameshifts are known to be pathogenic in this gene associated with Lynch syndrome (Stenson et al., 2014). The c.1743delA variant causes a frameshift starting with codon Glutamic acid 582, changes this amino acid to a Lysine residue, and creates a premature Stop codon at position 13 of the new reading frame, denoted p.Glu582LysfsX13. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1743delA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Based on the ACMG recommendations, c.1743delA is interpreted as an pathogenic variant.
Invitae RCV000551730 SCV000625556 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-06-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu582Lysfs*13) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related disease. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000561668 SCV000670745 pathogenic Hereditary cancer-predisposing syndrome 2018-01-17 criteria provided, single submitter clinical testing Other acmg-defined mutation (i.e. initiation codon or gross deletion);Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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