Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002417515 | SCV002725980 | uncertain significance | Inborn genetic diseases | 2018-03-12 | criteria provided, single submitter | clinical testing | The c.2113+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 10 in the CREBBP gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003101065 | SCV003449649 | uncertain significance | Rubinstein-Taybi syndrome | 2022-06-20 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 10 of the CREBBP gene. It does not directly change the encoded amino acid sequence of the CREBBP 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. 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 may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with CREBBP-related conditions. This variant is present in population databases (rs367714273, gnomAD 0.01%). |