ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.591C>T (p.Gly197=)

gnomAD frequency: 0.00004  dbSNP: rs748518694
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471455 SCV000551994 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-19 criteria provided, single submitter clinical testing This sequence change affects codon 197 of the PMS2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PMS2 protein. This variant is present in population databases (rs748518694, gnomAD 0.03%). This variant has been observed in individual(s) with PMS2-related conditions (PMID: 29596542). ClinVar contains an entry for this variant (Variation ID: 411048). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics RCV000571978 SCV000664750 likely benign Hereditary cancer-predisposing syndrome 2015-08-27 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.
Color Diagnostics, LLC DBA Color Health RCV000571978 SCV000691087 likely benign Hereditary cancer-predisposing syndrome 2021-09-08 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000571978 SCV002530363 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-27 criteria provided, single submitter curation
GeneDx RCV003151778 SCV003840631 uncertain significance not provided 2023-02-16 criteria provided, single submitter clinical testing In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Identified in the MMR-proficient tumor from an individual with colorectal cancer (Hampel et al., 2018); This variant is associated with the following publications: (PMID: 35451539, 29596542)

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