Submissions for variant NM_000251.2(MSH2):c.1886A>G (p.Gln629Arg) (rs61756468)

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076314	SCV000107335	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability <0.001
Invitae	RCV001079970	SCV000166267	benign	Hereditary nonpolyposis colorectal neoplasms	2019-12-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000121562	SCV000170345	benign	not specified	2014-05-05	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.
Ambry Genetics	RCV000129036	SCV000172946	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	In silico models in agreement (benign);Other data supporting benign classification;Other strong data supporting benign classification;Subpopulation frequency in support of benign classification
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center	RCV000490519	SCV000267400	uncertain significance	Lynch syndrome I	2016-03-18	criteria provided, single submitter	reference population
Illumina Clinical Services Laboratory,Illumina	RCV000490519	SCV000430930	likely benign	Lynch syndrome I	2017-04-27	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000121562	SCV000601445	likely benign	not specified	2016-10-12	criteria provided, single submitter	clinical testing
Color	RCV000129036	SCV000684992	benign	Hereditary cancer-predisposing syndrome	2015-02-02	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000587872	SCV000696228	benign	not provided	2016-09-06	criteria provided, single submitter	clinical testing	Variant summary: The MSH2 c.1886A>G (p.Gln629Arg) variant involves the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 159/123118 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.0174486 (151/8654). This frequency is about 31 times the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. This variant has also been reported in colorectal patients or HNPCC-related cancer without strong evidence for pathogenicity. In a family, while affected proband carried the variant, another affected cousin did not carry the variant, possibly suggesting that it did not co-segregate with disease in the family (Woo_2014). Multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as Benign.
PreventionGenetics,PreventionGenetics	RCV000121562	SCV000806016	benign	not specified	2017-08-02	criteria provided, single submitter	clinical testing
ITMI	RCV000121562	SCV000085756	not provided	not specified	2013-09-19	no assertion provided	reference population
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000121562	SCV000691907	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam	RCV000490519	SCV000745643	benign	Lynch syndrome I	2017-07-04	no assertion criteria provided	clinical testing