ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.819A>G (p.Val273=)

gnomAD frequency: 0.00086  dbSNP: rs146577635
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082291 SCV000166287 benign Hereditary nonpolyposis colorectal neoplasms 2021-12-15 criteria provided, single submitter clinical testing
GeneDx RCV000212592 SCV000211243 benign not specified 2014-09-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000160641 SCV000212735 likely benign Hereditary cancer-predisposing syndrome 2014-06-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000160641 SCV000685132 likely benign Hereditary cancer-predisposing syndrome 2015-10-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586418 SCV000696287 benign not provided 2016-02-23 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.819A>G variant affects a non-conserved nucleotide, resulting in no amino acid change. Mutation Taster predicts a damaging outcome for this variant, and 2/5 Alamut algorithms predict no significant change to normal splicing and no changes to ESE binding sites. The variant of interest has not been evaluated for functional impact by in vivo/vitro studies. This variant is found in 31/121148 control chromosomes at a frequency of 0.0002559, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0005683). However, the allele frequency in Africans (29/10308; 0.002813) is 5-fold greater than the maximal expected allele frequency for a pathogenic MSH2 variant, suggesting that this is a benign polymorphism found in Africans. In addition, clinical laboratories classified this variant as likely benign/benign. Taken together, this variant was classified as benign.
PreventionGenetics,PreventionGenetics RCV000586418 SCV000806050 likely benign not provided 2017-07-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586418 SCV000888235 benign not provided 2018-01-10 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001139365 SCV001299508 uncertain significance Lynch syndrome 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory,University of Chicago RCV000212592 SCV002071657 likely benign not specified 2017-10-25 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000160641 SCV002526751 benign Hereditary cancer-predisposing syndrome 2021-02-03 criteria provided, single submitter curation

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