Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165094 | SCV000215802 | likely benign | Hereditary cancer-predisposing syndrome | 2014-07-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Invitae | RCV000233469 | SCV000284093 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001704201 | SCV000530573 | likely benign | not provided | 2020-06-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000165094 | SCV000689959 | likely benign | Hereditary cancer-predisposing syndrome | 2017-04-24 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000663112 | SCV000786240 | likely benign | Lynch syndrome 1 | 2018-03-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000427878 | SCV001363059 | uncertain significance | not specified | 2019-12-15 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.115C>A alters a conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a cryptic exonic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.2e-05 in 226718 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.115C>A in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |
Myriad Genetics, |
RCV000663112 | SCV004018271 | benign | Lynch syndrome 1 | 2023-03-17 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001704201 | SCV004220937 | uncertain significance | not provided | 2023-08-09 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in individuals with MSH2-related conditions in the published literature. The frequency of this variant in the general population, 0.000051 (6/117294 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on MSH2 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant. |