ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1579_1580del (p.Arg527fs) (rs1064793234)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566950 SCV000663481 pathogenic Hereditary cancer-predisposing syndrome 2016-02-25 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)
Color RCV000566950 SCV000910444 pathogenic Hereditary cancer-predisposing syndrome 2018-02-23 criteria provided, single submitter clinical testing
GeneDx RCV000482204 SCV000565402 pathogenic not provided 2014-11-19 criteria provided, single submitter clinical testing This deletion of 2 nucleotides is denoted PMS2 c.1579_1580delAG at the cDNA level and p.Arg527GlyfsX14 (R527GfsX14) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GGAC[AG]GGGC. The deletion causes a frameshift, which changes an Arginine to a Glycine at codon 527, and creates a premature stop codon at position 14 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 RCV000699239 SCV000827940 pathogenic Hereditary nonpolyposis colon cancer 2018-02-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg527Glyfs*14) 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 in an individual affected with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 418417). 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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