Submissions for variant NM_000535.7(PMS2):c.2006+6G>A

gnomAD frequency: 0.04390  dbSNP: rs111905775

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076839	SCV000108327	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Eurofins Ntd Llc (ga)	RCV000079106	SCV000110975	benign	not specified	2018-03-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000130905	SCV000185814	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Color Diagnostics, LLC DBA Color Health	RCV000130905	SCV000292095	benign	Hereditary cancer-predisposing syndrome	2014-12-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079106	SCV000304726	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625384	SCV000469720	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	RCV001534380	SCV000604895	benign	not provided	2023-11-21	criteria provided, single submitter	clinical testing
Invitae	RCV000546054	SCV000625577	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625384	SCV000745187	benign	Lynch syndrome 4	2017-05-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000625384	SCV000785289	benign	Lynch syndrome 4	2017-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001534380	SCV001751304	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24710284)
Myriad Genetics, Inc.	RCV000625384	SCV004019869	benign	Lynch syndrome 4	2023-04-05	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000079106	SCV000257309	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354038	SCV000592942	benign	Endometrial carcinoma		no assertion criteria provided	clinical testing	“The PMS2, c.2006+6G>A variant was identified in 7% of 253542 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).”
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000079106	SCV001905833	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000079106	SCV001920265	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079106	SCV001957405	benign	not specified		no assertion criteria provided	clinical testing