Total submissions: 27
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076815 | SCV000108301 | no known pathogenicity | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | MAF >1% |
Ambry Genetics | RCV000162424 | SCV000212769 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | 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 |
RCV000121845 | SCV000225238 | benign | not specified | 2018-03-04 | criteria provided, single submitter | clinical testing | |
Vantari Genetics | RCV000162424 | SCV000267074 | likely benign | Hereditary cancer-predisposing syndrome | 2016-02-04 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000121845 | SCV000304722 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000625103 | SCV000469729 | likely benign | Lynch syndrome 4 | 2018-02-02 | 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Color Diagnostics, |
RCV000162424 | SCV000537382 | benign | Hereditary cancer-predisposing syndrome | 2014-11-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001083434 | SCV000562219 | benign | Hereditary nonpolyposis colorectal neoplasms | 2025-02-04 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000034618 | SCV000609635 | benign | not provided | 2017-04-19 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000625103 | SCV000743781 | benign | Lynch syndrome 4 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000034618 | SCV001156612 | benign | not provided | 2023-10-16 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000034618 | SCV001900688 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24728327, 27153395, 27884173, 24027009) |
Sema4, |
RCV000162424 | SCV002530200 | benign | Hereditary cancer-predisposing syndrome | 2020-08-07 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000121845 | SCV002550716 | benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003149611 | SCV003837732 | benign | Breast and/or ovarian cancer | 2021-06-30 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV000625103 | SCV004016584 | benign | Lynch syndrome 4 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000076815 | SCV004844190 | benign | Lynch syndrome | 2024-09-28 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000121845 | SCV004847562 | benign | not specified | 2021-06-10 | criteria provided, single submitter | clinical testing | The p.Thr511Met variant in PMS2 is classified as benign because it has been identified in 8.03% (2002/24922) of African chromosomes, including 81 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). In addition, computational prediction and conservation tools suggest that this variant does not impact the protein. ACMG/AMP Criteria applied: BA1, BP4. |
Biesecker Lab/Clinical Genomics Section, |
RCV000034618 | SCV000043426 | variant of unknown significance | not provided | 2012-07-13 | flagged submission | research | Converted during submission to Uncertain significance. |
ITMI | RCV000121845 | SCV000086045 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Genome Diagnostics Laboratory, |
RCV000625103 | SCV000745841 | benign | Lynch syndrome 4 | 2017-06-05 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000162424 | SCV000788104 | benign | Hereditary cancer-predisposing syndrome | 2018-01-12 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001357320 | SCV001552761 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The PMS2 p.Thr511Met variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was also identified in dbSNP (ID: rs74902811) as With other allele, ClinVar (classified as benign by InSight, Ambry Genetics, Prevention Genetics, Color Genimics, Invitae; classified as likely benign by Vantary genetics, Illumina), Clinvitae (classified with conflicting interpretations of pathogenicity), MutDB , Insight Colon Cancer Gene Variant Database (2X class1), Insight Hereditary Tumors Database (2X class1), databases. The variant was not identified in Cosmic, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, databases. The variant was identified in control databases in 2670(84 homozygous) of 277088 chromosomes at a frequency of 0.009636 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 1930 of 24008 chromosomes (freq: 0.08), EastAsian in 549 of 18862 chromosomes (freq: 0.029). In cell free assay by Drost (2013) the variant not classified as repair deficient and might be pathogenic with reduced penetrance. Tthe variant classified as benign by ACMG-AMP classification for consensus variants (Amendola 2016). The p.Thr511 residue is not conserved in mammals 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. The variant occurs outside of the splicing consensus sequence and 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 this variant meets our laboratory's criteria to be classified as benign. | |
Laboratory of Diagnostic Genome Analysis, |
RCV000121845 | SCV001799651 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000121845 | SCV001920671 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000121845 | SCV001959423 | benign | not specified | no assertion criteria provided | clinical testing | ||
Institute for Biomarker Research, |
RCV000162424 | SCV001977063 | benign | Hereditary cancer-predisposing syndrome | 2021-09-27 | no assertion criteria provided | clinical testing |