ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1408C>T (p.Pro470Ser) (rs1805321)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030364 SCV000108294 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research MAF >1%
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079103 SCV000110972 benign not specified 2018-04-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130721 SCV000185608 benign Hereditary cancer-predisposing syndrome 2014-07-14 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
Color Health, Inc RCV000130721 SCV000292075 benign Hereditary cancer-predisposing syndrome 2014-11-05 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000079103 SCV000304717 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000515612 SCV000469733 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282360 SCV000604897 benign none provided 2020-09-01 criteria provided, single submitter clinical testing
IntelligeneCG RCV000515612 SCV000611718 benign Hereditary nonpolyposis colorectal cancer type 4 2017-08-18 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000079103 SCV000711441 benign not specified 2017-04-20 criteria provided, single submitter clinical testing p.Pro470Ser in Exon 11 of PMS2: This variant is not expected to have clinical si gnificance because it has been identified in 45% (4560/10152) of Ashkenazi Jewis h chromosomes and 41% (52732/126656) of European chromosomes by the Genome Aggre gation Database (GnomAD, http://gnomad.broadinstitute.org; dbSNP rs1805321).
Counsyl RCV000515612 SCV000785318 benign Hereditary nonpolyposis colorectal cancer type 4 2017-07-06 criteria provided, single submitter clinical testing
Invitae RCV001080458 SCV001000261 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-01 criteria provided, single submitter clinical testing
GeneDx RCV000034614 SCV001845963 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034614 SCV000043430 no known pathogenicity not provided 2012-07-13 no assertion criteria provided research Converted during submission to Benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030364 SCV000053031 benign Lynch syndrome 2011-06-22 no assertion criteria provided clinical testing
ITMI RCV000079103 SCV000086042 not provided not specified 2013-09-19 no assertion provided reference population
Pathway Genomics RCV000144645 SCV000189972 benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353625 SCV000592934 benign Endometrial carcinoma no assertion criteria provided clinical testing The PMS2 p.Pro470Ser variant was identified in 464 of 1592 chromosomes (frequency: 0.294) from individuals with colorectal and/or endometrial cancer, suspected HNPCC and artherosclerosis (Borras_2013_2370975, Clendenning_2006_16619239, Gururangan_2008_17993636, He_2011_21984973, Hendriks_2006_16472587, Johnston_2012_22703879_supplementary, Kim_2004_15448003); however, control chromosomes were not analyzed in all of the studies, thus the prevalence of the variant in the general population could not be determined. The variant was also identified in dbSNP (ID: rs1805321) “With benign allele”, MutDB, and InSiGHT Colon Cancer DB. The variant was listed in the NHLBI Exome Sequencing Project in 3620 of 8600 European American alleles (frequency: 0.421) and in 1242 of 4856 African American alleles (frequency:0.256), increasing the likelihood that it may be a polymorphism in certain populations. The p.Pro470Ser variant is not conserved/conserved in mammals and 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. This variant is unlikely to have an effect on splicing as it is downstream of the exon/intron junction. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000079103 SCV000691974 benign not specified no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000079103 SCV001744259 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000079103 SCV001906094 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000079103 SCV001922389 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000079103 SCV001951485 benign not specified no assertion criteria provided clinical testing

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