ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.1783+5G>C (rs142082313)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212570 SCV000149819 likely benign not specified 2014-01-17 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.
Ambry Genetics RCV000115910 SCV000186079 benign Hereditary cancer-predisposing syndrome 2014-11-24 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
Invitae RCV001080166 SCV000253446 benign Ataxia-telangiectasia-like disorder 2020-12-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589610 SCV000698605 likely benign not provided 2017-06-16 criteria provided, single submitter clinical testing Variant summary: The MRE11A c.1783+5G>C variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict weakening effect on the canonical splicing donor site and ESEfinders predict change of ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 84/121382 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.007407 (77/10396). This frequency is about 119 times the estimated maximal expected allele frequency of a pathogenic MRE11A variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign until more evidence becomes available.
Athena Diagnostics Inc RCV000589610 SCV000842792 benign not provided 2019-01-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287216 SCV001473883 uncertain significance Ataxia-telangiectasia-like disorder 1 2020-02-14 criteria provided, single submitter clinical testing The MRE11 c.1783+5G>C variant (rs142082313), to our knowledge, is not reported in the medical literature but is reported as benign/likely benign in the ClinVar database (Variation ID: 127975). This variant is found in the African population with an allele frequency of 0.9% (224/24962 alleles, including 2 homozygotes) in the Genome Aggregation Database. This is an intronic variant in a moderately conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. However, these predictions have not been confirmed by functional studies. Due to limited information, the clinical significance of this variant is uncertain at this time.

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