ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1708A>G (p.Asn570Asp)

gnomAD frequency: 0.00048  dbSNP: rs115670442
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129033 SCV000172943 likely benign Hereditary cancer-predisposing syndrome 2018-12-28 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Invitae RCV000195850 SCV000253292 likely benign Hereditary nonpolyposis colorectal neoplasms 2021-12-17 criteria provided, single submitter clinical testing
GeneDx RCV001719888 SCV000279145 likely benign not provided 2021-06-22 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000121841 SCV000601827 likely benign not specified 2017-07-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000121841 SCV000697309 likely benign not specified 2019-02-01 criteria provided, single submitter clinical testing Variant summary: The variant, PMS2 c.1708A>G (p.Asn570Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 278512 control chromosomes, predominantly at a frequency of 0.0017 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 15 fold of the estimated maximal expected allele frequency for a pathogenic variant in PMS2 causing Lynch Syndrome phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1708A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Color Diagnostics, LLC DBA Color Health RCV000129033 SCV000910757 likely benign Hereditary cancer-predisposing syndrome 2016-02-25 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001164192 SCV001326301 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory,University of Chicago RCV000121841 SCV002067280 uncertain significance not specified 2019-04-26 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000129033 SCV002530221 likely benign Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter curation
ITMI RCV000121841 SCV000086039 not provided not specified 2013-09-19 no assertion provided reference population

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