Submissions for variant NM_000535.7(PMS2):c.1266G>A (p.Glu422=)

gnomAD frequency: 0.00348  dbSNP: rs138049175

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162549	SCV000212959	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: 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.
Eurofins Ntd Llc (ga)	RCV000174014	SCV000225239	benign	not specified	2015-02-18	criteria provided, single submitter	clinical testing
Invitae	RCV001080463	SCV000261980	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000174014	SCV000304716	benign	not specified		criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000174014	SCV000596476	benign	not specified	2017-06-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162549	SCV000686115	benign	Hereditary cancer-predisposing syndrome	2015-09-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587785	SCV000697287	benign	not provided	2016-02-01	criteria provided, single submitter	clinical testing	Variant summary: The c.1266G>A variant affects a non-conserved nucleotide, resulting in no amino acid change. One in-silico tool predicts damaging outcome for this variant. This variant is found in 116/120402 control chromosomes at a frequency of 0.0009634, which is about 8 times of maximal expected frequency of a pathogenic allele (0.0001136), suggesting this variant is benign. Sequence alignment suggests alleles identified in ExAC controls are unlikely from PMS2 pseudogenes. In addition, two clinical laboratories classified this variant as benign. Taken together, this variant was classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625105	SCV000743783	likely benign	Lynch syndrome 4	2017-03-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625105	SCV001324210	benign	Lynch syndrome 4	2018-04-05	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587785	SCV001472055	benign	not provided	2022-12-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000587785	SCV001745564	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149987	SCV003837738	benign	Breast and/or ovarian cancer	2021-07-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000625105	SCV004016601	benign	Lynch syndrome 4	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000174014	SCV004025120	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625105	SCV000745845	benign	Lynch syndrome 4	2017-06-05	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000162549	SCV000788100	likely benign	Hereditary cancer-predisposing syndrome	2017-09-29	no assertion criteria provided	clinical testing