ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1376C>G (p.Ser459Ter) (rs587780724)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439409 SCV000536465 pathogenic not provided 2017-01-23 criteria provided, single submitter clinical testing The S459X variant in the PMS2 gene has been reported in the homozygous state in at least one individual with a hematologic malignancy in childhood (Oberg et al., 2016). The S459X 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. This substitution is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on currently available evidence, we consider S459X to be pathogenic.
Invitae RCV000629760 SCV000750716 pathogenic Hereditary nonpolyposis colon cancer 2018-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser459*) 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 been reported as homozygous in an individual affected with T-cell lymphoblastic lymphoma (PMID: 28007021). ClinVar contains an entry for this variant (Variation ID: 393103). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.

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