ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2007-4G>A

gnomAD frequency: 0.12350  dbSNP: rs1805326
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Total submissions: 21
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076842 SCV000108330 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research MAF >1%
Eurofins Ntd Llc (ga) RCV000079107 SCV000110976 benign not specified 2014-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162400 SCV000212726 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: 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 RCV000857353 SCV000252713 benign Hereditary nonpolyposis colorectal neoplasms 2024-02-01 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV000079107 SCV000304727 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000605440 SCV000469718 benign Lynch syndrome 4 2018-01-13 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000079107 SCV000711444 benign not specified 2017-04-20 criteria provided, single submitter clinical testing c.2007-4G>A in intron 11 of PMS2: This variant is not expected to have clinical significance because it has been identified in 29% (3575/12334) of East Asian ch romosomes by the Genome Aggregation Database (GnomAD, http://gnomad.broadinstitu te.org; dbSNP rs1805326).
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000605440 SCV000745185 benign Lynch syndrome 4 2015-09-21 criteria provided, single submitter clinical testing
Counsyl RCV000605440 SCV000785193 benign Lynch syndrome 4 2017-06-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001650894 SCV001156610 benign not provided 2023-11-30 criteria provided, single submitter clinical testing
GeneDx RCV001650894 SCV001867003 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000605440 SCV004016579 benign Lynch syndrome 4 2023-07-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000605440 SCV004019870 benign Lynch syndrome 4 2023-04-05 criteria provided, single submitter clinical testing This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Color Diagnostics, LLC DBA Color Health RCV000162400 SCV004359574 benign Hereditary cancer-predisposing syndrome 2015-03-31 criteria provided, single submitter clinical testing
Pathway Genomics RCV000144647 SCV000189974 benign Lynch syndrome 1 2014-07-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001353429 SCV000592944 benign Endometrial carcinoma no assertion criteria provided clinical testing PMS2, INTRON 11, c.2007-4G>A, p.?, (Alias:IVS11-4G>A ), Benign (ACMG 5) The PMS2 c.2007-4G>A variant was identified in 51 of 306 proband chromosomes (frequency: 0.167) from individuals or families with Hereditary Non-Polyposis Colon Cancer (16472587_Hendriks_2006, 16619239_clendenning_2006); 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 also identified in dbSNP (ID: rs140788589) “With benign allele”, with a minor allele frequency of 0.1627 (1000 Genomes Project), “InSiGHT Colon Cancer Database”, and the ClinVar database. The variant was classified as a benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The c.2007-4G>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.) In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000079107 SCV000691962 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000605440 SCV000734560 benign Lynch syndrome 4 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute RCV000079107 SCV001906150 benign not specified no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000079107 SCV001921259 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000079107 SCV001955940 benign not specified no assertion criteria provided clinical testing

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