ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.1475C>A (p.Ala492Asp) (rs61749249)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000114897 SCV000149816 likely benign not provided 2020-12-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28051113, 26898890, 26483394, 30666157)
Ambry Genetics RCV000115907 SCV000172746 benign Hereditary cancer-predisposing syndrome 2014-08-07 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Genetic Services Laboratory, University of Chicago RCV000193395 SCV000248073 uncertain significance not specified 2014-06-27 criteria provided, single submitter clinical testing
Invitae RCV001079570 SCV000253443 benign Ataxia-telangiectasia-like disorder 2020-12-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000193395 SCV000341540 likely benign not specified 2016-04-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000524517 SCV000604243 uncertain significance Ataxia-telangiectasia-like disorder 1 2020-03-27 criteria provided, single submitter clinical testing The MRE11 c.1475C>A; p.Ala492Asp variant (rs61749249) is reported in the literature in individuals with hereditary breast and ovarian cancer syndrome, colon cancer, or pancreatic cancer (Caminsky 2016, Castellanos 2017, Hu 2016). However, this variant is also found in the general population with an overall allele frequency of 0.3% (961/282780 alleles, including 3 homozygotes) in the Genome Aggregation Database. This variant is reported in the ClinVar database (Variation ID: 127031). The alanine at codon 492 is moderately conserved, but computational analyses (SIFT: Tolerated, PolyPhen-2: Possibly Damaging) predict conflicting effects of this variant on protein structure/function. Based on available information, the clinical significance of this variant is uncertain at this time. References: Caminsky NG et al. Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations. Hum Mutat. 2016 Jul;37(7):640-52. Castellanos E et al. A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape. Sci Rep. 2017 Jan 4;7:39348. Hu C et al. Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients. Cancer Epidemiol Biomarkers Prev. 2016 Jan;25(1):207-11.
Counsyl RCV000524517 SCV000785308 likely benign Ataxia-telangiectasia-like disorder 1 2017-07-05 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000193395 SCV000842789 benign not specified 2020-01-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000114897 SCV001148387 likely benign not provided 2021-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000524517 SCV001271758 benign Ataxia-telangiectasia-like disorder 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Baylor Genetics RCV000524517 SCV001483058 uncertain significance Ataxia-telangiectasia-like disorder 1 2018-11-30 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Harris Lab, University of Minnesota RCV000114897 SCV000148792 not provided not provided no assertion provided not provided
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000114897 SCV001799829 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000114897 SCV001929018 likely benign not provided no assertion criteria provided clinical testing

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