Submissions for variant NM_000251.3(MSH2):c.1511-41G>C

gnomAD frequency: 0.00038  dbSNP: rs202215396

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455376	SCV000539694	uncertain significance	not specified	2016-12-14	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This is an intronic variant. The variant has been reported in one patient with a sebaceous adenoma whose mother had CRC at age 56. Staining of MSH2 in the tumor was normal (Everett 2014). This variant is present in ExAC at a MaxMAF of 0.04% (30 alleles) and in gnomAD at 0.05% (68 alleles). It is classified in ClinVar as likely benign by Invitae (1 star).
GeneDx	RCV000455376	SCV000728521	likely benign	not specified	2018-01-10	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl	RCV000663053	SCV000786103	likely benign	Lynch syndrome 1	2018-02-28	criteria provided, single submitter	clinical testing
Mendelics	RCV000663053	SCV001135733	benign	Lynch syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812214	SCV001477906	likely benign	not provided	2019-10-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001520677	SCV001729845	benign	Hereditary nonpolyposis colorectal neoplasms	2023-05-10	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257512	SCV002534377	likely benign	Hereditary cancer-predisposing syndrome	2020-12-07	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000455376	SCV002552232	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001812214	SCV005050296	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	MSH2: BP1, BP4
PreventionGenetics, part of Exact Sciences	RCV004529007	SCV004103642	likely benign	MSH2-related disorder	2023-11-15	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).