Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001017391 | SCV001178466 | likely benign | Hereditary cancer-predisposing syndrome | 2024-01-24 | 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 |
RCV001055942 | SCV001220357 | uncertain significance | Rhabdoid tumor predisposition syndrome 2 | 2023-08-05 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 6 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. This variant is present in population databases (rs747149353, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 822216). 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. 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. |
Genome- |
RCV001809913 | SCV002056419 | uncertain significance | Intellectual disability, autosomal dominant 16 | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478630 | SCV004220377 | uncertain significance | not provided | 2023-09-18 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000087 (3/34592 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect SMARCA4 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant. |