ClinVar Miner

Submissions for variant NM_005591.4(MRE11):c.845+2T>A

dbSNP: rs587781381
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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 RCV000129209 SCV000183959 likely pathogenic Hereditary cancer-predisposing syndrome 2022-12-09 criteria provided, single submitter clinical testing The c.845+2T>A intronic variant results from a T to A substitution two nucleotides after coding exon 7 of the MRE11 gene. This alteration was identified in an individual who underwent hereditary cancer multi-gene panel testing (LaDuca H et al. Genet. Med., 2014 Nov;16:830-7). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Eurofins Ntd Llc (ga) RCV000397709 SCV000336958 pathogenic not provided 2015-11-06 criteria provided, single submitter clinical testing
Invitae RCV002228305 SCV002509429 likely pathogenic Ataxia-telangiectasia-like disorder 2023-07-10 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 140936). Disruption of this splice site has been observed in individual(s) with clinical features of hereditary cancer syndrome(s) who underwent multigene panel testing (PMID: 24763289). This sequence change affects a donor splice site in intron 8 of the MRE11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MRE11 are known to be pathogenic (PMID: 23080121, 23912341). This variant is present in population databases (rs587781381, gnomAD 0.003%).

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