ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.851del (p.Ser283_Ser284insTer) (rs876658964)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215549 SCV000274855 pathogenic Hereditary cancer-predisposing syndrome 2016-07-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
GeneDx RCV000479888 SCV000569360 pathogenic not provided 2016-02-09 criteria provided, single submitter clinical testing This deletion of one nucleotide is denoted PMS2 c.851delC at the cDNA level and p.Ser284Ter (S284X) at the protein level. The normal sequence, with the base that is deleted in braces, is AGTT[C]AACA. The deletion creates a nonsense variant, which changes a Serine to a premature stop codon. Although this variant has not been previously reported to our knowledge, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000589130 SCV000697391 likely pathogenic Lynch syndrome 2017-07-10 criteria provided, single submitter clinical testing Variant summary: The PMS2 c.851delC (p.Ser284X) variant results in a premature termination codon, predicted to cause a truncated or absent PMS2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.861_864delACAG, p.Arg287fsX19; c.1021delA, p.Arg341fsX15; c.1164delT, p.His388fsX10). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121008 control chromosomes and has been reported in the literature in a cohort of individuals being tested by a multi-gene panel, with no phenotype data provided for the individual carrying the variant (Espenschied_2017). Multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.

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