ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2400A>G (p.Leu800=) (rs201298777)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212619 SCV000211253 benign not specified 2014-08-25 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 RCV000160651 SCV000212862 likely benign Hereditary cancer-predisposing syndrome 2014-06-03 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724817 SCV000226006 uncertain significance not provided 2015-05-27 criteria provided, single submitter clinical testing
Invitae RCV001083867 SCV000253155 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000410686 SCV000430935 uncertain significance Lynch syndrome I 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.
Counsyl RCV000410686 SCV000489650 likely benign Lynch syndrome I 2016-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160651 SCV000690070 likely benign Hereditary cancer-predisposing syndrome 2015-07-27 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000410686 SCV000744281 likely benign Lynch syndrome I 2017-06-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212619 SCV000919695 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354589 SCV001549238 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH2 p.Leu800= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs201298777) as "With other allele ", ClinVar (classified as benign by GeneDx; as likely benign by Ambry Genetics, Invitae, Counsyl, and Color; and as uncertain significance by three submitters), and in UMD-LSDB (1x as neutral). The variant was identified in control databases in 14 of 277180 chromosomes at a frequency of 0.00005 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 14 of 126676 chromosomes (freq: 0.0001), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Leu800= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer,) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics,Academic Medical Center RCV000724817 SCV001920688 likely benign not provided no assertion criteria provided clinical testing

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