Total submissions: 20
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076241 | SCV000107260 | likely benign | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Synonymous substitution with no effec on splicing, tested with NMD inhibitor |
Gene |
RCV000212605 | SCV000170343 | benign | not specified | 2013-12-18 | 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 | RCV000126817 | SCV000212795 | likely benign | Hereditary cancer-predisposing syndrome | 2014-07-07 | 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 |
RCV001081918 | SCV000253152 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000986677 | SCV000430929 | uncertain significance | Lynch syndrome 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Color Diagnostics, |
RCV000126817 | SCV000684966 | benign | Hereditary cancer-predisposing syndrome | 2015-07-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587483 | SCV000696222 | benign | not provided | 2016-06-27 | criteria provided, single submitter | clinical testing | Variant summary: The MSH2 c.1680T>C (p.Asn560Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splicing algorithms predict no change to normal splicing, and ex vivo splicing assay showed this variant does not affect splicing. This variant was found in 42/120644 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0006173 (41/66422). This frequency is greater than 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 European (Non-Finnish) origin. In addition, the variant was found to co-occur with a pathogenic MSH2 variant, c.1079T>A (p.Leu360X), in one individual reported by UMD. Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as Benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212605 | SCV000889422 | benign | not specified | 2021-12-03 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000986677 | SCV001135740 | likely benign | Lynch syndrome 1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000587483 | SCV001152278 | likely benign | not provided | 2021-05-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000212605 | SCV002071318 | likely benign | not specified | 2019-10-08 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000126817 | SCV002534394 | benign | Hereditary cancer-predisposing syndrome | 2021-06-08 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000212605 | SCV002552237 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498367 | SCV002808553 | likely benign | Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2 | 2022-03-16 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003149748 | SCV003838305 | likely benign | Breast and/or ovarian cancer | 2022-05-05 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000076241 | SCV004834070 | benign | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355862 | SCV001550868 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The MSH2 p.Asn560= variant was identified in the literature however the frequency of this variant in an affected population was not provided (Tournier 2008). The variant was also identified in the following databases: dbSNP (ID: rs200056411) as With Likely benign allele, ClinVar (classified as benign by GeneDx, Invitae; as likely benign by Insight, Ambry Genetics), Clinvitae (classified as benign by ClinVar; as likely benign by Invitae), UMD-LSDB (6X as neutral), Insight Colon Cancer Gene Variant Database (8X Class2), and the Insight Hereditary Tumors Database (8X Class2). The variant was not identified in COGR, Zhejiang Colon Cancer Database, and Mismatch Repair Genes Variant Database. In UMD the variant was identified with a co-occurring pathogenic MSH2 variant (c.1079T>A (p.Leu360X)), increasing the likelihood that the p.Asn560= variant does not have clinical significance. The variant was identified in control databases in 81 of 276170 chromosomes at a frequency of 0.0003 in the following populations: EuropeanNon-Finnish in 71 of 126188 chromosomes (freq. 0.001), EuropeanFinnish in 6 of 25786 chromosomes (freq. 0.0002), Latino in 2 of 34356 chromosomes (freq.0.0001), African in 1 of 24008 chromosomes (freq. 0.00004), Other in 1 of 6452 chromosomes (freq. 0.0002), increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). Functional analysis using the pCAS ex vivo splicing assay demonstrated this variant had no effect (Tournier 2008). The p.Asn560= 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, HumanSpliceFinder) 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. | |
Genome Diagnostics Laboratory, |
RCV000587483 | SCV001807293 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000587483 | SCV001905768 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000587483 | SCV001968429 | likely benign | not provided | no assertion criteria provided | clinical testing |