ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1532C>T (p.Thr511Met) (rs74902811)

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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) 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 General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics 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
PreventionGenetics,PreventionGenetics RCV000121845 SCV000304722 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000625103 SCV000469729 likely benign Hereditary nonpolyposis colorectal cancer type 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 Health, Inc RCV000162424 SCV000537382 benign Hereditary cancer-predisposing syndrome 2014-11-12 criteria provided, single submitter clinical testing
Invitae RCV001083434 SCV000562219 benign Hereditary nonpolyposis colorectal neoplasms 2020-11-23 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000034618 SCV000609635 benign not provided 2017-04-19 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000625103 SCV000743781 benign Hereditary nonpolyposis colorectal cancer type 4 2014-10-09 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000625103 SCV000745841 benign Hereditary nonpolyposis colorectal cancer type 4 2017-06-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282355 SCV001156612 benign none provided 2020-05-05 criteria provided, single submitter clinical testing
GeneDx 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)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034618 SCV000043426 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000121845 SCV000086045 not provided not specified 2013-09-19 no assertion provided reference population
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,Sinai Health System 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, Leiden University Medical Center (LUMC) RCV000121845 SCV001799651 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000121845 SCV001920671 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000121845 SCV001959423 benign not specified no assertion criteria provided clinical testing

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