Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076619 | SCV000107654 | likely benign | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability 0.001-0.049 |
Gene |
RCV000212588 | SCV000149444 | likely benign | not specified | 2017-09-05 | 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. |
Invitae | RCV001086693 | SCV000166283 | benign | Hereditary nonpolyposis colorectal neoplasms | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000115535 | SCV000183948 | likely benign | Hereditary cancer-predisposing syndrome | 2018-11-30 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign);Subpopulation frequency in support of benign classification;Co-occurence with mutation in same gene (phase unknown);Does not segregate with disease in family study (genes with incomplete penetrance) |
Color | RCV000115535 | SCV000537440 | likely benign | Hereditary cancer-predisposing syndrome | 2015-02-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212588 | SCV000601482 | benign | not specified | 2017-06-22 | criteria provided, single submitter | clinical testing | |
Center for Human Genetics, |
RCV000659879 | SCV000781770 | uncertain significance | Lynch syndrome I | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759836 | SCV000889441 | benign | not provided | 2017-06-22 | criteria provided, single submitter | clinical testing | |
Cancer Genomics Group, |
RCV001030707 | SCV001193629 | likely benign | Hereditary breast and ovarian cancer syndrome | 2019-05-01 | criteria provided, single submitter | research | |
Illumina Clinical Services Laboratory, |
RCV000659879 | SCV001297031 | likely benign | Lynch syndrome I | 2018-02-27 | 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. |
Integrated Genetics/Laboratory Corporation of America | RCV000212588 | SCV001360857 | benign | not specified | 2019-11-26 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.505A>G (p.Ile169Val) results in a conservative amino acid change located in the DNA mismatch repair protein MutS, connector domain (IPR007860) of 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 0.00047 in 251484 control chromosomes, predominantly at a frequency of 0.0064 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 11 fold of the estimated maximal expected allele frequency for a pathogenic variant in MSH2 causing Lynch Syndrome phenotype (0.00057), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.505A>G has been reported in the literature in individuals affected with colon cancer and gastric cancer (Tomita_2003, Park_2008, Kim_2017). These reports do not provide unequivocal conclusions about association of the variant with Lynch Syndrome. Additionally, Park_2008 reports that this variant did not co-segregate with disease in one family. Co-occurrence with a pathogenic variant has been reported (MSH2 c.905T>A, p.Leu302Ter) (Tomita_2003), providing supporting evidence for a benign role. At least one publication reports this variant showed no damaging effect of this variant (Zhu_2013). Six ClinVar submitters including one expert panel (InSiGHT, classified as likely benign in 2013) (evaluation after 2014) cite the variant as uncertain significance (1x), likely benign (3x) and benign (2x). Based on the evidence outlined above, the variant was classified as benign. |