Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000588331 | SCV000149615 | uncertain significance | not provided | 2023-10-20 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25980754, 26517685, 24728327, 26689913, 28503720, 11574484, 28726808, 31992580, 34680242) |
Ambry Genetics | RCV000115706 | SCV000216880 | likely benign | Hereditary cancer-predisposing syndrome | 2021-03-22 | 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. |
Invitae | RCV000197094 | SCV000254618 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000409948 | SCV000488997 | uncertain significance | Lynch syndrome 4 | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000115706 | SCV000686246 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 286 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with breast, pancreatic, ovarian and colorectal cancer and/or polyps (PMID: 28503720, 26689913, 26517685, 25980754, 28726808, 31391288, 34680242, 33471991) and in healthy individuals (PMID: 24728327, 33471991). Two of these individuals, one affected with ovarian cancer and the other suspected of Lynch syndrome, also had a pathogenic MSH6 co-variant (PMID: 26689913, 26517685). This variant has been identified in 36/282838 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Mendelics | RCV000708992 | SCV000838189 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588331 | SCV000888418 | uncertain significance | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals affected with a Lynch syndrome-associated cancer (PMID: 31391288 (2020), 25980754 (2015)), breast cancer (PMID: 28503720 (2017)), colorectal cancer (PMID: 35430768 (2022), 34680242 (2021), 31992580 (2020)), ovarian cancer (PMID: 26689913 (2015)), pancreatic cancer (PMID: 28726808 (2018)), endometrial cancer (PMID 26517685 (2015)), and acute myeloid leukemia (PMID: 30760869 (2019)). In a large breast cancer association study, this variant was reported in individuals affected with breast cancer as well as unaffected individuals (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/PMS2)). The frequency of this variant in the general population, 0.0002 (26/129148 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Fulgent Genetics, |
RCV000765960 | SCV000897381 | uncertain significance | Mismatch repair cancer syndrome 1; Lynch syndrome 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001798338 | SCV002042817 | uncertain significance | Breast and/or ovarian cancer | 2021-01-04 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000409948 | SCV004019791 | likely benign | Lynch syndrome 4 | 2023-04-04 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. Homozygosity for this variant has been confirmed in one or more individuals lacking clinical features consistent with gene-specific recessive disease, indicating that this variant is unlikely to be pathogenic. |
Baylor Genetics | RCV000409948 | SCV004205340 | uncertain significance | Lynch syndrome 4 | 2023-10-30 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000708992 | SCV004839898 | uncertain significance | Lynch syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 286 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with breast, pancreatic, ovarian and colorectal cancer and/or polyps (PMID: 28503720, 26689913, 26517685, 25980754, 28726808, 31391288, 34680242, 33471991) and in healthy individuals (PMID: 24728327, 33471991). Two of these individuals, one affected with ovarian cancer and the other suspected of Lynch syndrome, also had a pathogenic MSH6 co-variant (PMID: 26689913, 26517685). This variant has been identified in 36/282838 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
ITMI | RCV000121861 | SCV000086063 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Pathway Genomics | RCV000144656 | SCV000189983 | uncertain significance | Lynch syndrome 1 | 2014-07-24 | no assertion criteria provided | clinical testing | |
Genome |
RCV003326121 | SCV001749542 | not provided | Lynch syndrome; Mismatch repair cancer syndrome 4 | no assertion provided | phenotyping only | ||
Genome Diagnostics Laboratory, |
RCV000588331 | SCV001808752 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000588331 | SCV001954994 | uncertain significance | not provided | no assertion criteria provided | clinical testing |