Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002229362 | SCV000288935 | uncertain significance | Ataxia-telangiectasia-like disorder | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change affects codon 521 of the MRE11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MRE11 protein. This variant also falls at the last nucleotide of exon 14, which is part of the consensus splice site for this exon. This variant is present in population databases (rs779250359, gnomAD 0.01%). 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: 240185). Variants that disrupt 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. 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. |
| Ambry Genetics | RCV001012138 | SCV001172559 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-20 | criteria provided, single submitter | clinical testing | The c.1563G>A variant (also known as p.E521E), located in coding exon 13 of the MRE11A gene, results from a G to A substitution at nucleotide position 1563. This nucleotide substitution does not change the amino acid at codon 521. However, this change occurs in the last base pair of coding exon 13, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |