Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003066455 | SCV003445992 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-09-10 | criteria provided, single submitter | clinical testing | 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 2138899). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 31 of the SMARCA4 gene. It does not directly change the encoded amino acid sequence of the SMARCA4 protein. It affects a nucleotide within 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 | RCV003340600 | SCV004059302 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The c.4521-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 31 in the SMARCA4 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |