ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.477G>A (p.Val159=)

gnomAD frequency: 0.00006  dbSNP: rs147701251
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163908 SCV000214502 likely benign Hereditary cancer-predisposing syndrome 2014-08-18 criteria provided, single submitter clinical testing This alteration is classified as likely 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 RCV001085711 SCV000253302 likely benign Hereditary nonpolyposis colorectal neoplasms 2021-12-17 criteria provided, single submitter clinical testing
Counsyl RCV000411054 SCV000489639 likely benign Colorectal cancer, hereditary nonpolyposis, type 4 2016-11-08 criteria provided, single submitter clinical testing
GeneDx RCV000435221 SCV000514193 benign not specified 2015-03-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color Diagnostics, LLC DBA Color Health RCV000163908 SCV000537468 likely benign Hereditary cancer-predisposing syndrome 2015-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000198465 SCV001134603 likely benign not provided 2019-04-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000435221 SCV001361985 benign not specified 2019-12-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000435221 SCV002067557 likely benign not specified 2020-03-04 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000163908 SCV002530347 likely benign Hereditary cancer-predisposing syndrome 2021-02-17 criteria provided, single submitter curation
True Health Diagnostics RCV000163908 SCV000788116 likely benign Hereditary cancer-predisposing syndrome 2018-01-24 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358290 SCV001553982 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The PMS2 p.Val159= variant was not identified in the literature nor was it identified in the following databases: COGR, Clinvitae, Cosmic, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, or the Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs147701251) “With Likely benign allele”, ClinVar (classified as benign by GeneDx and likely benign by Ambry Genetics, Invitae, Counsyl and Color Genomics Inc), and in control databases in 21 of 276590 chromosomes at a frequency of 0.00008 increasing the likelihood this could be a low frequency variant (Genome Aggregation Consortium Feb 27, 2017). The observations by population include Latino in 3 of 34398 chromosomes (freq: 0.00009), European Non-Finnish in 14 of 126292 chromosomes (freq: 0.0001), and South Asian in 4 of 30766 chromosomes (freq:0.0001); the variant was not observed in African, Ashkenazi Jewish, East Asian, and European Finnish populations. The p.Val159= 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.

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