Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clinical Genomics Laboratory, |
RCV005001939 | SCV005627204 | uncertain significance | Coffin-Siris syndrome 8 | 2022-02-10 | criteria provided, single submitter | clinical testing | The p.Lys236Asn variant in the SMARCC2 gene has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The lysine at position 236 is evolutionarily conserved. The p.Lys236Asn variant occurs at the 5’ splice junction of exon 8 and computational tools predict an impact to splicing. However, the accuracy of these computational tools is limited. The SMARCC2 gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Lys236Asn variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PM2; PP3] |