ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.965G>A (p.Gly322Asp) (rs4987188)

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Total submissions: 26
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030257 SCV000107802 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research MAF >1% & Multifactorial likelihood analysis posterior probability <0.001
Invitae RCV001083998 SCV000153907 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000121567 SCV000170332 benign not specified 2013-09-27 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 RCV000157760 SCV000212730 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Vantari Genetics RCV000157760 SCV000267049 benign Hereditary cancer-predisposing syndrome 2015-12-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000157760 SCV000292106 benign Hereditary cancer-predisposing syndrome 2014-11-26 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000030257 SCV000296897 benign Lynch syndrome 2015-11-30 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000121567 SCV000303167 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000144615 SCV000430919 likely benign Lynch syndrome I 2018-03-06 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000121567 SCV000604258 benign not specified 2019-03-15 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000144615 SCV000743208 benign Lynch syndrome I 2017-07-28 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000144615 SCV000744271 benign Lynch syndrome I 2015-09-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000144615 SCV000745635 benign Lynch syndrome I 2015-08-07 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262750 SCV001440732 likely benign Breast carcinoma 2019-01-01 criteria provided, single submitter clinical testing
OMIM RCV000001832 SCV000021988 benign MSH2 POLYMORPHISM 1998-11-01 no assertion criteria provided literature only
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034561 SCV000043338 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030257 SCV000052924 benign Lynch syndrome 2015-04-08 no assertion criteria provided clinical testing
ITMI RCV000121567 SCV000085762 not provided not specified 2013-09-19 no assertion provided reference population
Pathway Genomics RCV000144615 SCV000189942 benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000121567 SCV000257200 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353916 SCV000592482 benign Carcinoma of colon no assertion criteria provided clinical testing The p.Gly322Asp variant has been identified in 78 out of 3532 proband chromosomes (frequency 0.022) in individuals with endometrial and colorectal cancer phenotypes, however it is also found in 69 out of 2790 control chromosomes (frequency 0.025), increasing the likelihood that this is a benign variant (Barneston 2008, Christensen 2008, Aceto 2009, Hampel 2006, Kurzawski 2006, Raptis 2005, Valentin 2011, Pastrello 2011, Sven Arnold_2009). It is listed in dbSNP database (ID#: rs4987188) with an average heterozygosity of 0.019+/-0.096 in various human populations, further suggesting the benign nature of this variant. The p.Gly322 is highly conserved in mammals and other species, however in silico computational analysis (Sift, PolyPhen and AlignGVGD) do not suggest an impact on the protein function, therefore increasing the likelihood of this variant to be benign. Although functional impact for the yeast homolog (yMSH2–G317D) have been suggeested by earlier yeast assays (Drotschmann 1999; Ellison 2001), recent studies did not implicate any functional impact associated with the p.Gly322Asp variant (Wielders 2011, Kansikas 2011, Ollila 2008). In summary, based on the above information this variant is classified as Benign.
True Health Diagnostics RCV000157760 SCV000788040 benign Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000121567 SCV001797363 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000121567 SCV001906032 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000121567 SCV001919760 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000121567 SCV001956602 benign not specified no assertion criteria provided clinical testing

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