ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2567A>G (p.Tyr856Cys) (rs587779150)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662430 SCV000784885 uncertain significance Lynch syndrome I 2017-02-08 criteria provided, single submitter clinical testing
Invitae RCV000692140 SCV000819949 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-05-24 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 856 of the MSH2 protein (p.Tyr856Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs587779150, ExAC 0.009%). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827) and the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 91003). An algorithm developed specifically for the MSH2 gene suggests that this missense change is likely to be tolerated (PMID: 26333163). However, this prediction has not been confirmed by published functional studies and its clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000774582 SCV000908331 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-06 criteria provided, single submitter clinical testing
Division of Medical Genetics, University of Washington RCV000662430 SCV001434266 uncertain significance Lynch syndrome I 2019-11-25 criteria provided, single submitter clinical testing To our knowledge, this sequence variant has not been previously reported in the literature. This variant has an overall allele frequency of 0.000004 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). In silico analyses indicate that this variant does not alter protein structure/function. Thus, it is unknown at this time whether this variant increases cancer risk. PM2; BP4

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