ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1557T>C (p.Tyr519=) (rs6972869)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130271 SCV000185116 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174013 SCV000225237 benign not specified 2014-08-06 criteria provided, single submitter clinical testing
Invitae RCV000524438 SCV000262045 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000205619 SCV000469728 likely benign Hereditary nonpolyposis colorectal cancer type 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.
Color Health, Inc RCV000130271 SCV000686138 benign Hereditary cancer-predisposing syndrome 2015-04-22 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000174013 SCV000806178 benign not specified 2017-02-02 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000130271 SCV000788105 likely benign Hereditary cancer-predisposing syndrome 2017-10-26 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357173 SCV001552547 benign Malignant tumor of breast no assertion criteria provided clinical testing The PMS2 p.Tyr519= variant was identified in 1 of 792 proband chromosomes (frequency: 0.001) from Dutch individuals or families with MMR-deficient cancer, or positive family history/young age of onset for CRC, endometrial or other Lynch associated cancer (van der Klift_2016_27435373). In this study, the variant showed no mRNA aberratiom or allelic imbalance using cultured lymphocytes. The variant was also identified in dbSNP (ID: rs6972869) “With other allele”, ClinVar (classified benign by Ambry Genetics, EGL Genetic Diagnostics (Eurofins Clinical Diagnostics) and Invitae, and likely benign by Illumina), and Clinvitae (4x), but was not identified in Genesight-COGR, Cosmic, MutDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in control databases in 867 (15 homozygous) of 277080 chromosomes at a frequency of 0.003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 824 (15 homozygous) of 23990 chromosomes (freq: 0.03), Other in 8 of 6464 chromosomes (freq: 0.001), Latino in 25 of 34418 chromosomes (freq: 0.0007), European Non-Finnish in 10 of 126632 chromosomes (freq: 0.00008), while not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The p.Tyr519= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.