Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001021683 | SCV001183330 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-11-27 | criteria provided, single submitter | clinical testing | The c.402+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 4 of the MRE11A gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. 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. |
| Invitae | RCV002549542 | SCV003453023 | likely pathogenic | Ataxia-telangiectasia-like disorder | 2023-12-26 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 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 (no rsID available, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with MRE11-related conditions. ClinVar contains an entry for this variant (Variation ID: 824512). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Baylor Genetics | RCV003467663 | SCV004193851 | likely pathogenic | Ataxia-telangiectasia-like disorder 1 | 2023-05-03 | criteria provided, single submitter | clinical testing |