Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002830793 | SCV003614155 | likely benign | Inborn genetic diseases | 2022-09-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV003777817 | SCV004650622 | uncertain significance | Cornelia de Lange syndrome 4 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change affects codon 540 of the RAD21 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RAD21 protein. This variant also falls at the last nucleotide of exon 12, which is part of the consensus splice site for this exon. This variant is present in population databases (rs746050594, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with RAD21-related conditions. ClinVar contains an entry for this variant (Variation ID: 2281575). 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. |