Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164645 | SCV000215309 | likely benign | Hereditary cancer-predisposing syndrome | 2014-05-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
| Labcorp Genetics |
RCV000205248 | SCV000259807 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2025-01-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000442945 | SCV000513657 | benign | not specified | 2015-07-14 | 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. |
| Color Diagnostics, |
RCV000164645 | SCV000684907 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-02 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001815239 | SCV002063854 | likely benign | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing | MSH2: BP4, BP7 |
| Sema4, |
RCV000164645 | SCV002528813 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-06 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV003995356 | SCV004827154 | likely benign | Lynch syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000442945 | SCV005076039 | likely benign | not specified | 2024-04-27 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV005246709 | SCV005897143 | benign | Lynch syndrome 1 | 2024-12-06 | 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. |
| Department of Pathology and Laboratory Medicine, |
RCV001357506 | SCV001552994 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The MSH2 p.Gln377= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs181852377) as “With Likely benign allele”, ClinVar (classified as benign by GeneDx and as likely benign by Ambry Genetics, Invitae and Color), and UMD-LSDB (1x classified UV). The variant was identified in control databases in 12 of 246238 chromosomes at a frequency of 0.00005 (Genome Aggregation Database Feb 27, 2017), observed in the following populations: European Non-Finnish in 5 of 111690 chromosomes (freq: 0.00005), East Asian in 4 of 17248 chromosomes (freq: 0.0002), and South Asian in 3 of 30780 chromosomes (freq: 0.0001), while not observed in the African, Other, Latino, Ashkenazi Jewish, or European Finnish populations. The p.Gln377= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |