ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.738C>G (p.Pro246=)

gnomAD frequency: 0.00005  dbSNP: rs202094399
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206202 SCV000259771 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-12-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000220152 SCV000274699 likely benign Hereditary cancer-predisposing syndrome 2015-03-19 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.
Counsyl RCV000409744 SCV000488364 likely benign Lynch syndrome 4 2016-03-08 criteria provided, single submitter clinical testing
GeneDx RCV001722117 SCV000520403 likely benign not provided 2021-05-17 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000220152 SCV000686232 likely benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000430291 SCV000697383 likely benign not specified 2023-07-31 criteria provided, single submitter clinical testing Variant summary: PMS2 c.738C>G alters a conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 248942 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.738C>G in individuals affected with Hereditary Nonpolyposis Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Sema4, Sema4 RCV000220152 SCV002530382 likely benign Hereditary cancer-predisposing syndrome 2022-02-17 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000409744 SCV004019814 benign Lynch syndrome 4 2023-04-04 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001722117 SCV004219025 likely benign not provided 2023-09-14 criteria provided, single submitter clinical testing

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