Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002342647 | SCV002642702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-01 | criteria provided, single submitter | clinical testing | The c.4935_4944del10 variant, located in coding exon 34 of the SMARCA4 gene, results from a deletion of 10 nucleotides at nucleotide positions 4935 to 4944, causing a translational frameshift with a predicted alternate stop codon (p.R1646Afs*10). This alteration occurs at the 3' terminus of theSMARCA4 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 34 amino acids of the protein. The exact functional effect of this alteration is unknown. Loss-of-function variants in SMARCA4 are known to cause rhabdoid tumor predisposition syndrome including small cell carcinoma of the ovary-hypercalcemic type (SCCOHT); however, such associations with neurodevelopmental disorders are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Jelinic P et al. Nat Genet. 2014 May;46(5):424-6). Based on the supporting evidence, the association of this alteration with rhabdoid tumor predisposition syndrome is unknown; however, the association of this alteration with Coffin-Siris syndrome is unlikely. |
| Labcorp Genetics |
RCV003102654 | SCV003009428 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2022-05-21 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1646Alafs*10) in the SMARCA4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the SMARCA4 protein. |