ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1420G>T (p.Ala474Ser) (rs373114291)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123078 SCV000166373 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131575 SCV000186583 likely benign Hereditary cancer-predisposing syndrome 2018-06-27 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign)
GeneDx RCV000479914 SCV000565404 uncertain significance not provided 2021-07-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Observed in individuals with a history of a Lynch syndrome-associated tumor and/or polyps and other cancers (Yurgelun 2015, Zhang 2015, Blount 2018); This variant is associated with the following publications: (PMID: 29286535, 25980754, 26580448)
Color Health, Inc RCV000131575 SCV000686125 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-09 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 474 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with Lynch syndrome–associated cancer and/or polyps (PMID: 25980754) and breast cancer (PMID: 29286535). This variant has also been identified in 6/251492 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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