ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.823C>G (p.Gln275Glu) (rs587780062)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130089 SCV000184918 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-24 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000411073 SCV000487933 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2015-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000486746 SCV000565389 uncertain significance not provided 2018-10-01 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.823C>G at the cDNA level, p.Gln275Glu (Q275E) at the protein level, and results in the change of a Glutamine to a Glutamic Acid (CAA>GAA). This variant was observed in at least one individual with a personal and/or family history suggestive of Lynch syndrome (van der Klift 2015). PMS2 Gln275Glu was observed at an allele frequency of 0.03% (8/25,794) in individuals of Finnish ancestry in large population cohorts (Lek 2016). This variant is located in ATPase domain (Guarne 2001). While protein-based in silico analysis supports that this variant does not alter protein structure/function, splicing models predict the creation of a novel splice site. Additionally, van der Klift et al. (2015) reported this variant to cause splicing defects in a minigene assay, leading to two aberrant transcripts due to use of cryptic splice acceptor sites. Based on currently available evidence, it is unclear whether PMS2 Gln275Glu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130089 SCV000686243 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-02 criteria provided, single submitter clinical testing
Invitae RCV001079273 SCV000751218 likely benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing

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