ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.1798G>C (p.Glu600Gln)

gnomAD frequency: 0.00103  dbSNP: rs145415033
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131661 SCV000186688 likely benign Hereditary cancer-predisposing syndrome 2018-12-10 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV001081514 SCV000253447 likely benign Ataxia-telangiectasia-like disorder 2021-12-13 criteria provided, single submitter clinical testing
Eurofins NTD LLC (GA) RCV000731881 SCV000859749 uncertain significance not provided 2018-03-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781549 SCV000919682 benign not specified 2018-10-29 criteria provided, single submitter clinical testing Variant summary: MRE11A c.1798G>C (p.Glu600Gln) 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 0.00029 in 276710 control chromosomes (including 1 homozygote), predominantly within the African subpopulation with a frequency of 0.003 in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 50 fold above the estimated maximal expected allele frequency for a pathogenic variant in MRE11A causing Hereditary Breast and Ovarian Cancer phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. In addition, the variant was reported in 21/2559 African American women (i.e. with a frequency of 0.0082), who were older than 70 years of age, and never had cancer (in the FLOSSIES database). To our knowledge, no occurrence of c.1798G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services,Illumina RCV001112603 SCV001270279 uncertain significance Ataxia-telangiectasia-like disorder 1 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.
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State RCV002225446 SCV002504802 likely benign Hereditary breast ovarian cancer syndrome 2022-04-19 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000131661 SCV002538408 likely benign Hereditary cancer-predisposing syndrome 2022-01-30 criteria provided, single submitter curation

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