Total submissions: 27
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076832 | SCV000108319 | no known pathogenicity | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | MAF >1% |
Invitae | RCV001083359 | SCV000153961 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000121850 | SCV000171035 | benign | not specified | 2013-10-14 | 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. |
Ambry Genetics | RCV000131477 | SCV000186464 | benign | Hereditary cancer-predisposing syndrome | 2017-12-08 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Genomic Diagnostic Laboratory, |
RCV000076832 | SCV000257702 | benign | Lynch syndrome | 2015-06-18 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131477 | SCV000292103 | benign | Hereditary cancer-predisposing syndrome | 2022-01-02 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000121850 | SCV000304725 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000615283 | SCV000469725 | likely benign | Lynch syndrome 4 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Laboratory for Molecular Medicine, |
RCV000121850 | SCV000540063 | benign | not specified | 2016-03-28 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: High frequency |
Genome Diagnostics Laboratory, |
RCV000615283 | SCV000743777 | likely benign | Lynch syndrome 4 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000615283 | SCV000745189 | benign | Lynch syndrome 4 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000034623 | SCV000884395 | benign | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV001262164 | SCV001439937 | benign | Neoplasm of ovary | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000131477 | SCV002530236 | benign | Hereditary cancer-predisposing syndrome | 2020-05-04 | criteria provided, single submitter | curation | |
Ce |
RCV000034623 | SCV002545493 | benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | PMS2: BP4, BS1, BS2 |
Center for Genomic Medicine, |
RCV000121850 | SCV002550701 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034623 | SCV000043417 | no known pathogenicity | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Benign. |
ITMI | RCV000121850 | SCV000086051 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Department of Pathology and Laboratory Medicine, |
RCV001353875 | SCV000592941 | benign | Endometrial carcinoma | no assertion criteria provided | clinical testing | PMS2, Exon 11, c.1866G>A, p.Met622Ile, Benign, ACMG 5rnThe c.1866G>A variant was identified 10 times in 1950 proband chromosomes in the literature. This variant was found in tumors that are positive for microsatellite instability, negative for immunohistocompatibility complexes and negative for the BRAF gene (17312306_lagerstedt_robinson_2007). It was also found to be negative for PMS2 staining in two independent research papers (15256438_nakagawa_2004, 16472587_hendriks_2006)) and to be MLH1, MSH2, and MSH6 positive (15256438_nakagawa_2004). Berginc found that this missense change is in a region responsible for the interaction of PMS2 with MLH1 and it reduces binding to MLH1 in functional analysis. It was not found in healthy controls (19526325_berginc_2009). In all the literature it was speculated not to be pathogenic (24689082_Hansen_2014, 22949387_thompson_2013, 19526325_berginc_2009, 17312306_lagerstedt_robinson_2007, 16472587_hendriks_2006, 15256438_nakagawa_2004, 11793469_yuan_2002) rnThe variant was also identified in dbSNP (ID: rs1805324) “With untested allele”, with a minor allele frequency of 0.0082 (1000 Genomes Project), HGMD, COSMIC, “Mismatch Repair Genes Variant Database”, and ClinVar database as a benign/likely benign variant. It was submitted to ClinVar 6 times by single and independent submitters as a benign variant. rnThis variant was identified in the 1000 Genomes Project in 32 of 2178 chromosomes (frequency: 0.0147), Exome Variant Server project in 182 of 8600 European American (frequency: 0.021) and 23 of 4406 African American alleles (frequency: 0.0052), increasing the likelihood that this is/may be a low frequency benign variant in certain populations of origin.rnThe p.Met622 residue is not conserved in mammals and five out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein.rnThe c.1866G>A variant occurs outside of the splicing consensus sequence and in silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) does not predict a difference in splicing in 5 of 5 different programs. (However, this information is not predictive enough to rule out pathogenicity.)rnIn summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. | |
Mayo Clinic Laboratories, |
RCV000121850 | SCV000691964 | benign | not specified | no assertion criteria provided | clinical testing | ||
Diagnostic Laboratory, |
RCV000615283 | SCV000734562 | benign | Lynch syndrome 4 | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000615283 | SCV000745837 | benign | Lynch syndrome 4 | 2015-10-05 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000131477 | SCV000788112 | likely benign | Hereditary cancer-predisposing syndrome | 2017-12-01 | no assertion criteria provided | clinical testing | |
Laboratory of Diagnostic Genome Analysis, |
RCV000121850 | SCV001798352 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000121850 | SCV001905809 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000121850 | SCV001922233 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000121850 | SCV001952606 | benign | not specified | no assertion criteria provided | clinical testing |