Submissions for variant NM_000535.7(PMS2):c.396A>G (p.Gly132=)

dbSNP: rs786201073

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162534	SCV000212935	likely benign	Hereditary cancer-predisposing syndrome	2016-03-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	RCV000559233	SCV000625650	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162534	SCV001360034	likely benign	Hereditary cancer-predisposing syndrome	2020-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001785483	SCV002028117	likely benign	not provided	2021-05-17	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162534	SCV002530341	likely benign	Hereditary cancer-predisposing syndrome	2022-02-18	criteria provided, single submitter	curation
All of Us Research Program, National Institutes of Health	RCV003995200	SCV004842110	likely benign	Lynch syndrome	2023-06-27	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354316	SCV001548902	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The PMS2 p.Gly132= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Clinvitae, MutDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, Insight Hereditary Tumors Database, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The variant was identified in dbSNP (ID: rs786201073) “With Likely benign allele”, ClinVar (classified likely benign by Ambry Genetics and Invitae), and Cosmic (4x in liver neoplasm). The p.Gly132= 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.