ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.877A>G (p.Asn293Asp) (rs530993704)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131778 SCV000186825 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-28 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238840 SCV000296938 uncertain significance Lynch syndrome 2015-10-13 criteria provided, single submitter clinical testing
Counsyl RCV000410031 SCV000488705 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2016-05-27 criteria provided, single submitter clinical testing
Invitae RCV000524482 SCV000551931 uncertain significance Hereditary nonpolyposis colon cancer 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 293 of the PMS2 protein (p.Asn293Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs530993704, ExAC 0.02%). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 142577). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000486344 SCV000567284 uncertain significance not provided 2018-12-17 criteria provided, single submitter clinical testing This variant is denoted PMS2 c.877A>G at the cDNA level, p.Asn293Asp (N293D) at the protein level, and results in the change of an Asparagine to an Aspartic Acid (AAC>GAC). This variant was observed in at least one individual with breast cancer (Tung 2015). PMS2 Asn293Asp was not observed at a significant allele frequency in large population cohorts (Lek 2016). PMS2 Asn293Asp is located within the ATPase domain (Guarne 2001). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether PMS2 Asn293Asp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000131778 SCV000803170 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486344 SCV000888420 uncertain significance not provided 2017-10-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765959 SCV000897380 uncertain significance Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 4 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000131778 SCV000909669 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-12 criteria provided, single submitter clinical testing

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