Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001377592 | SCV001574963 | likely pathogenic | Rhabdoid tumor predisposition syndrome 2 | 2020-05-14 | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SMARCA4 are known to be pathogenic (PMID: 24658001, 24658002). This variant has not been reported in the literature in individuals with SMARCA4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 26 of the SMARCA4 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Ambry Genetics | RCV002350724 | SCV002623498 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-02 | criteria provided, single submitter | clinical testing | The c.3774+2T>A intronic variant results from a T to A substitution two nucleotides after coding exon 25 in the SMARCA4 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. |