ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2271C>T (p.Tyr757=) (rs56076152)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163040 SCV000213530 likely benign Hereditary cancer-predisposing syndrome 2014-11-07 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.
Invitae RCV001080852 SCV000253154 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163040 SCV000685029 likely benign Hereditary cancer-predisposing syndrome 2016-05-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759113 SCV000888219 benign not provided 2018-04-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001140259 SCV001300498 uncertain significance Lynch syndrome I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001358733 SCV001554578 likely benign not specified 2021-03-31 criteria provided, single submitter clinical testing
GeneDx RCV000759113 SCV001889241 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357863 SCV001553454 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH2 p.Tyr757= variant was not identified in the literature nor was it identified in the COGR, Cosmic, Zhejiang University Database, Mismatch Repair Genes Variant Database, and in Insight Hereditary Tumors databases. The variant was identified in dbSNP (ID: rs56076152) as "With Likely benign allele", ClinVar (classified as likely benign by Ambry Genetics, Invitae, Color Genomics), and in UMD-LSDB (1x as unclassified variant), databases. The variant was identified in control databases in 30 of 277180 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 3 of 24034 chromosomes (freq: 0.0001), Other in 2 of 6462 chromosomes (freq: 0.0003), Latino in 2 of 34420 chromosomes (freq: 0.00006), European in 6 of 126688 chromosomes (freq: 0.000047), Ashkenazi Jewish in 6 of 10152 chromosomes (freq: 0.00059), East Asian in 11 of 18870 chromosomes (freq: 0.00058), while the variant was not observed in the Finnish, and South Asian populations. The p.Tyr757= 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, HumanSpliceFinder) 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.

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