ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.688_689GT[1] (p.Phe231fs) (rs1064795447)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479977 SCV000571255 pathogenic not provided 2016-08-16 criteria provided, single submitter clinical testing This deletion of two nucleotides in PMS2 is denoted c.690_691delGT at the cDNA level and p.Phe231TrpfsX17 (F231WfsX17) at the protein level. The normal sequence, with the bases that are deleted in braces, is CTGT[GT]TTGG. The deletion causes a frameshift which changes a Phenylalanine to a Tryptophan at codon 231, and creates a premature stop codon at position 17 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Invitae RCV000539605 SCV000625672 pathogenic Hereditary nonpolyposis colon cancer 2017-03-01 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotide from exon 6 of the PMS2 mRNA (c.690_691delGT), causing a frameshift at codon 231. This creates a premature translational stop signal (p.Phe231Trpfs*17) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Color RCV001183707 SCV001349513 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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