Submissions for variant NM_000251.3(MSH2):c.2615A>G (p.Lys872Arg)

dbSNP: rs587780686

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000122987	SCV000166275	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-09-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000411448	SCV000488337	uncertain significance	Lynch syndrome 1	2016-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000563636	SCV000669775	likely benign	Hereditary cancer-predisposing syndrome	2018-09-07	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.
Color Diagnostics, LLC DBA Color Health	RCV000563636	SCV001347193	uncertain significance	Hereditary cancer-predisposing syndrome	2019-03-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002469017	SCV002765983	uncertain significance	not specified	2022-11-10	criteria provided, single submitter	clinical testing	Variant summary: MSH2 c.2615A>G (p.Lys872Arg) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251424 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2615A>G has been reported in the literature in individuals affected pancreatic and ovarian cancer (example: Hu_2016 and Pal_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=1) and VUS (n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149838	SCV003837631	uncertain significance	Breast and/or ovarian cancer	2021-10-29	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000411448	SCV004018347	uncertain significance	Lynch syndrome 1	2023-03-21	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV003997407	SCV004826564	uncertain significance	Lynch syndrome	2023-10-02	criteria provided, single submitter	clinical testing