Submissions for variant NM_000535.7(PMS2):c.2570G>C (p.Gly857Ala)

gnomAD frequency: 0.30966  dbSNP: rs1802683

Total submissions: 22

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030370	SCV000108358	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Eurofins Ntd Llc (ga)	RCV000079109	SCV000110978	benign	not specified	2018-04-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000130363	SCV000185215	benign	Hereditary cancer-predisposing syndrome	2014-10-22	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Invitae	RCV001079827	SCV000252720	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079109	SCV000304733	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625382	SCV000469714	benign	Lynch syndrome 4	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034628	SCV000604890	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625382	SCV000745183	benign	Lynch syndrome 4	2015-09-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000625382	SCV000785321	benign	Lynch syndrome 4	2017-07-06	criteria provided, single submitter	clinical testing
Mendelics	RCV000625382	SCV001137275	benign	Lynch syndrome 4	2019-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000034628	SCV001753923	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000079109	SCV002069904	benign	not specified	2022-01-18	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130363	SCV002530321	benign	Hereditary cancer-predisposing syndrome	2021-11-28	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000625382	SCV004044377	benign	Lynch syndrome 4	2023-05-11	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Color Diagnostics, LLC DBA Color Health	RCV000130363	SCV004358947	benign	Hereditary cancer-predisposing syndrome	2014-11-04	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034628	SCV000043413	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030370	SCV000053037	benign	Lynch syndrome	2013-11-20	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000144646	SCV000189973	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353501	SCV000592955	benign	Endometrial carcinoma		no assertion criteria provided	clinical testing	The PMS2 p.Gly857Ala variant was identified in 28% of 213820 control alleles in the Genome Aggregation Consortium (February 27, 2017). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015).”
Mayo Clinic Laboratories, Mayo Clinic	RCV000079109	SCV000691955	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000079109	SCV001922688	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079109	SCV001957131	benign	not specified		no assertion criteria provided	clinical testing