[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-354834-105":59,"doc-detail-354834-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","characterization-of-a-novel-msh2-variant-in-lynch-syndrome-clinical-data-and-complementary-bioinformatics-assessment","Characterization of a novel MSH2 variant in Lynch syndrome - clinical data and complementary bioinformatics assessment","","The study characterizes a novel MSH2 germline variant, NM_000251.3(MSH2):c.1894_1898del (p.Ile633Lysfs*9), identified in a family with Lynch syndrome. Clinical assessment documented phenotype and family history, alongside immunohistochemical evaluation of the proband’s tumors. Pathogenicity classification followed ACMG/AMP criteria using a multi-step bioinformatics workflow: database and literature screening, computational impact prediction, and exploration of compensatory mechanisms such as alternative splicing, exon skipping, and nonsense-mediated decay. Results indicate a frameshift that generates a premature stop codon consistent with likely pathogenicity.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/characterization-of-a-novel-msh2-variant-in-lynch-syndrome-clinical-data-and-complementary-bioinformatics-assessment/354834/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/characterization-of-a-novel-msh2-variant-in-lynch-syndrome-clinical-data-and-complementary-bioinformatics-assessment/354834.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What novel genetic variant is investigated in the study?","Question",{"text":112,"@type":113},"The article investigates a novel MSH2 germline variant, NM_000251.3(MSH2):c.1894_1898del (p.Ile633Lysfs*9).","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were clinical features and tumor findings assessed?",{"text":117,"@type":113},"Clinical evaluation described the phenotype and family history, and immunohistochemistry characterized the proband’s tumors. The results showed loss of MSH2 expression in one tumor and loss of MSH2 and MSH6 in the other.",{"name":119,"@type":110,"acceptedAnswer":120},"Which bioinformatics approaches were used to evaluate pathogenicity?",{"text":121,"@type":113},"The study applied ACMG/AMP criteria supported by multi-step bioinformatics: variant screening in literature/databases, computational prediction of impacts, and assessment of potential mitigating mechanisms including alternative splicing/exon skipping and nonsense-mediated decay.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},354834,1790736670,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","Official Publication of the Instituto Israelita de Ensino e Pesquisa Albert Einstein  \nCharacterization of a novel MSH2 variant in Lynch syndrome: clinical data and complementary bioinformatics assessment  \n❚ Authors  \nAnisse Marques Chami, Thalia Rodrigues de Souza Zózimo, Carolina Guimarães Ramos Matosinho, Agnaldo Lopes da Silva-Filho, Maria Raquel Santos Carvalho, Letícia da Conceição Braga  \n❚ Correspondence  \n[E-mail: ma.raquel.carvalho@gmail.com](E-mail: ma.raquel.carvalho@gmail.com)  \n❚ DOI  \nDOI: 10.31744/einstein_journal/2026AO0757  \n❚ In Brief  \nFamilial cancer is a complex condition requiring genetic counseling. Screening for genetic variants is necessary in addition to clinical diagnosis. An identified genetic variant must be classified according to its potential pathogenicity. We identified a novel variant in the MSH2 gene, in a family with clinical manifestations compatible with Lynch Syndrome. Bioinformatics analysis showed that the variant created a frameshift mutation, leading to a premature stop codon. No compensatory mechanism was identified, confirming that this variant as likely pathogenic.  \n❚ Highlights  \n■ Family identified with recurrent colorectal cancer, suggestive of Lynch syndrome.  \n■ A new variant was detected, NM_000251.3(MSH2):c.1894 _ 1898del (p. Ile633Lysfs*9) .  \n■ The variant causes a frameshift mutation leading to a premature stop codon, suggesting pathogenicity.  \n■ Using bioinformatics tools, we investigated possible escape mechanisms, such as the presence of isoforms without the mutated exon.  \n■ Location of the variant suggests that it causes non-sense mediated decay, which is reinforced by immunohistochemistry findings showing absence of MSH2 protein expression.  \n■ Detailed assessment allows this variant to be classified as probably pathogenic/pathogenic.  \n❚ How to cite this article:  \nChami AM, Zózimo TR, Matosinho CG, Silva-Filho AL, Carvalho MR, Braga LC. Characterization of a novel MSH2 variant in Lynch syndrome: clinical data and complementary bioinformatics assessment. einstein (São Paulo) . 2026;24:eAO0757 .  \neinstein (São Paulo)  \nOR IG INAL ARTICLE  \nOfficial Publication of the Instituto Israelita de Ensino e Pesquisa Albert Einstein  \ne-ISSN: 2317-6385  \nHow to cite this article:  \nChami AM, Zózimo TR, Matosinho CG, Silva-Filho AL, Carvalho MR, Braga LC. Characterization of a novel MSH2 variant in Lynch syndrome: clinical data and complementary bioinformatics assessment. einstein (São Paulo) . 2026;24:eAO0757 .  \nData from the article was extracted from the thesis by author Anisse Marques Chami presented to the Faculdade de Medicina of the Universidade Estadual Paulista “Júlio de Mesquita Filho”, Botucatu Campus, to obtain the title of Doctor from the Graduate Program in Obstetrics and Gynecology, Concentration Area: Oncology, in 2022.  \nAssociate Editor:  \nKenneth Gollob  \nHospital Israelita Albert Einstein, São Paulo, SP, Brazil  \nORCID: [https://orcid.org/0000-0003-4184-3867](https://orcid.org/0000-0003-4184-3867)  \nCorresponding Author:  \nMaria Raquel Santos Carvalho  \nAvenida Antônio Carlos, 6627 ICB-E3175 Zip code: 31270-901-Belo Horizonte, MG, Brazil  \nPhone: (55 31) 3409-2598  \n[E-mail: ma.raquel.carvalho@gmail.com](E-mail: ma.raquel.carvalho@gmail.com)  \nReceived on:  \nMar 8, 2024  \nAccepted on:  \nJune 9, 2025  \nConflict of interest:  \nnone.  \nCopyright the authors  \nThis content is licensed  \nunder a Creative Commons Attribution 4.0 International License.  \nORIGINAL ARTICLE  \nCharacterization of a novel MSH2 variant in Lynch syndrome:  \nclinical data and complementary bioinformatics assessment  \nAnisse Marques Chami1, Thalia Rodrigues de Souza Zózimo2, Carolina Guimarães Ramos Matosinho2, Agnaldo Lopes da Silva-Filho 3, Maria Raquel Santos Carvalho2, Letícia da Conceição Braga4,5  \n1 Postgraduate Program in Obstetrics and Gynecology, Faculdade de Medicina, Universidade Estadual Paulista “Júlio de Mesquita Filho”, Botucatu, SP, Brazil.  \n2 Department of Genetics","cbCaid791f0CZU3g","https://ap.wps.com/l/cbCaid791f0CZU3g","pdf",1941037,12,"English","# In Brief\n# Highlights\n# Abstract\n## Objective\n## Methods\n## Results","[{\"question\":\"What novel genetic variant is investigated in the study?\",\"answer\":\"The article investigates a novel MSH2 germline variant, NM_000251.3(MSH2):c.1894_1898del (p.Ile633Lysfs*9).\"},{\"question\":\"How were clinical features and tumor findings assessed?\",\"answer\":\"Clinical evaluation described the phenotype and family history, and immunohistochemistry characterized the proband’s tumors. The results showed loss of MSH2 expression in one tumor and loss of MSH2 and MSH6 in the other.\"},{\"question\":\"Which bioinformatics approaches were used to evaluate pathogenicity?\",\"answer\":\"The study applied ACMG/AMP criteria supported by multi-step bioinformatics: variant screening in literature/databases, computational prediction of impacts, and assessment of potential mitigating mechanisms including alternative splicing/exon skipping and nonsense-mediated decay.\"}]","Characterization of a novel MSH2 variant in Lynch syndrome - clinical data and complementary bioinformatics assessment | PDF",1790114326]