ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1067del (p.Lys356fs) (rs587781395)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129239 SCV000183997 pathogenic Hereditary cancer-predisposing syndrome 2015-03-07 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 RCV000486460 SCV000566328 pathogenic not provided 2018-04-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in PMS2 is denoted c.1067delA at the cDNA level and p.Lys356ArgfsX4 (K356RfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is TTAA[delA]GACC. The deletion causes a frameshift, which changes a Lysine to an Arginine at codon 356, and creates a premature stop codon at position 4 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. PMS2 c.1067delA has been reported in at least three individuals with colon cancer, two of whom had tumors demonstrating absence of PMS2 protein expression on immunohistochemistry, and was also reported in at least one individual with endometrial and breast cancer (Cragun 2014, Goodenberger 2016, Rosty 2016). We consider this variant to be pathogenic.

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