Total submissions: 27
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076814 | SCV000108300 | no known pathogenicity | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | MAF >1% |
Labcorp Genetics |
RCV001083612 | SCV000153912 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000121839 | SCV000171027 | benign | not specified | 2013-09-03 | 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 | RCV000130845 | SCV000185743 | benign | Hereditary cancer-predisposing syndrome | 2014-10-14 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Eurofins Ntd Llc |
RCV000121839 | SCV000225235 | benign | not specified | 2014-10-28 | criteria provided, single submitter | clinical testing | |
Vantari Genetics | RCV000130845 | SCV000267075 | likely benign | Hereditary cancer-predisposing syndrome | 2015-12-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000130845 | SCV000292101 | benign | Hereditary cancer-predisposing syndrome | 2022-01-02 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000121839 | SCV000304721 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000625104 | SCV000469730 | likely benign | Lynch syndrome 4 | 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Genome Diagnostics Laboratory, |
RCV000625104 | SCV000743782 | benign | Lynch syndrome 4 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000625104 | SCV000745191 | benign | Lynch syndrome 4 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000625104 | SCV000785347 | benign | Lynch syndrome 4 | 2017-07-07 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000034617 | SCV001156613 | benign | not provided | 2023-11-28 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000121839 | SCV002550717 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000625104 | SCV004016580 | benign | Lynch syndrome 4 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000625104 | SCV004043729 | benign | Lynch syndrome 4 | 2023-05-11 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. |
All of Us Research Program, |
RCV000076814 | SCV004844191 | benign | Lynch syndrome | 2024-09-30 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034617 | SCV000043427 | no known pathogenicity | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Benign. |
ITMI | RCV000121839 | SCV000086037 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Department of Pathology and Laboratory Medicine, |
RCV001353895 | SCV000592936 | benign | Endometrial carcinoma | no assertion criteria provided | clinical testing | PMS2, EXON11, c.1531A>G, p.Thr511Ala, Benign (ACMG 5) The c.1531A>G variant was identified in 6 of 368 proband chromosomes (frequency: 0.016) from individuals or families with HNPCC and Lynch syndrome; however, control chromosomes were not evaluated in these studies, thus the prevalence of this variant in the general population could not be determined. The variant was present in individuals that tested immunohistocompatibility PMS2 negative but positive for MLH1, MSH2 and MSH 6. Tumours were also found to be microsatellite instability high. (10479499_Basil_1999, 15256438_Nakagawa, 16619239_Clenndening_2006, 24027009_Drost_2013) The variant was also identified in dbSNP (ID: rs2228007) “With untested allele”, with a minor allele frequency of 0.011 (1000 Genomes Project), “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, “InSiGHT Colon Cancer Database”, and ClinVar database as a benign variant.The variant was classified as a benign/likely benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports) with 6 separate submitters. The variant was classified as “unclassified” by a clinical laboratory within the Canadian Open Genetics Repository (http://opengenetics.ca/). This variant was identified in the 1000 Genomes Project in 26 of 2178 chromosomes (frequency: 0.0119), Exome Variant Server project in 270 of 13006 European American/African American alleles (frequency: 0.02), increasing the likelihood that this is/may be a low frequency benign variant in certain populations of origin. The p.Thr511 residue is not conserved in mammals and the variant amino acid Threonine (Thr) is present in Macaques and Trichoplax adhaerens, and four 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 but it increases the likelihood that this variant does not have clinical significance. The c.1531A>G 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.) In summary, based on the above information, the clinical significance of this variant satisfies our laboratory requirements as benign. | |
Mayo Clinic Laboratories, |
RCV000121839 | SCV000691971 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000625104 | SCV000745842 | benign | Lynch syndrome 4 | 2015-11-22 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000130845 | SCV000788103 | benign | Hereditary cancer-predisposing syndrome | 2018-02-05 | no assertion criteria provided | clinical testing | |
Laboratory of Diagnostic Genome Analysis, |
RCV000121839 | SCV001797728 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000121839 | SCV001906405 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000121839 | SCV001923712 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000121839 | SCV001951347 | benign | not specified | no assertion criteria provided | clinical testing |