ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.2070+2T>A (rs786202801)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165802 SCV000216549 likely pathogenic Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Dr. Peter K. Rogan Lab,Western University RCV000416696 SCV000262590 likely pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-22 no assertion criteria provided research Sequenced patient with familial breast cancer
Invitae RCV000642458 SCV000764137 uncertain significance Ataxia-telangiectasia-like disorder 2018-07-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 19) of the MRE11 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast cancer (PMID: 26898890, 24894818). ClinVar contains an entry for this variant (Variation ID: 186243). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Aberrant splicing at the C-terminal end of the MRE11 protein is expected to affect the DNA binding domain 2 (residues 654-708) (PMID: 9845372, 24894818). However, the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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