Submissions for variant NM_000179.3(MSH6):c.457+13A>G

gnomAD frequency: 0.00434  dbSNP: rs1800933

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000074991	SCV000108208	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability 0.001-0.049
GeneDx	RCV000202213	SCV000170369	benign	not specified	2013-10-28	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.
Vantari Genetics	RCV000126840	SCV000267053	benign	Hereditary cancer-predisposing syndrome	2015-12-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000202213	SCV000302880	benign	not specified		criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000126840	SCV000537388	benign	Hereditary cancer-predisposing syndrome	2015-04-06	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000126840	SCV000679732	likely benign	Hereditary cancer-predisposing syndrome	2017-07-12	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000611257	SCV000744286	benign	Lynch syndrome 5	2015-09-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000611257	SCV001135785	likely benign	Lynch syndrome 5	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000202213	SCV001158616	benign	not specified	2019-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000611257	SCV001300596	likely benign	Lynch syndrome 5	2018-02-22	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV002055074	SCV002365515	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000202213	SCV002552276	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001572716	SCV002585788	benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	MSH6: BS1, BS2
Ambry Genetics	RCV000126840	SCV002636066	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149728	SCV003837637	benign	Breast and/or ovarian cancer	2021-06-22	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000611257	SCV004015991	likely benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000202213	SCV000257300	likely benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353859	SCV000592568	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The c.457+13A>G variant has been previously reported in the literature in individuals with CRC (8/295 chromosomes) but the frequency in controls did not differ significantly from the cases tested (6/185 chromosomes) (Peterlongo_2003_14520694, Woods_2005_16203774). This variant was listed in dbSNP (rs1800933) 'with untested allele' and reported from the 1000 genomes 4 times (MAF of 0.002) The exome variant server reported this variant in a European cohort with the following frequency increasing the likelihood this variant does not have clinical significance: G=54/A=8546. Further, this variant does not occur within the splicing consensus sequence increasing the likelihood this variant does not have clinical significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000611257	SCV000734209	likely benign	Lynch syndrome 5		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000611257	SCV000745647	benign	Lynch syndrome 5	2016-10-07	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572716	SCV001797513	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000202213	SCV001906026	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000202213	SCV001922705	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000202213	SCV001956698	benign	not specified		no assertion criteria provided	clinical testing