Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000232807 | SCV000284090 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001705240 | SCV000518232 | likely benign | not provided | 2020-03-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000417988 | SCV000696198 | uncertain significance | not specified | 2019-04-18 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.1077-7A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.4e-05 in 280074 control chromosomes (gnomAD). 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.1077-7A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genetic Services Laboratory, |
RCV000417988 | SCV002066866 | uncertain significance | not specified | 2021-02-15 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV002258835 | SCV002528808 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-09 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001705240 | SCV004220935 | uncertain significance | not provided | 2023-07-27 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00017 (4/24174 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 splicing yielded predictions that this variant does not affect MSH2 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |
Prevention |
RCV004541370 | SCV004784810 | likely benign | MSH2-related disorder | 2020-02-25 | criteria provided, single submitter | 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). |
All of Us Research Program, |
RCV003998749 | SCV004818120 | likely benign | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing |