Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000194747 | SCV000248682 | uncertain significance | not specified | 2015-04-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000767032 | SCV000709981 | uncertain significance | not provided | 2018-02-20 | criteria provided, single submitter | clinical testing | The c.2455-4 T>G splice site variant in the RBBP8 gene has been reported previously as a homozygous variant in an individual with arthrogryposis multiplex, hypo/akinesia, pterygium, micrognathia, cleft palate, and hygroma (Laquerriere et al., 2014). The c.2455-4 T>G variant is observed in 26/111606 (0.2%) alleles from individuals of European background (Lek et al., 2016). This variant is predicted to reduce the quality of the splice acceptor site in intron 17. Functional studies demonstrate skipping of the adjacent exon 18, leading to a frameshift and stop codon (Laquerriere et al., 2014). Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000767032 | SCV002285058 | uncertain significance | not provided | 2022-06-20 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 17 of the RBBP8 gene. It does not directly change the encoded amino acid sequence of the RBBP8 protein. This variant is present in population databases (rs374660795, gnomAD 0.02%). This variant has been observed in individual(s) with arthrogryposis multiplex congenita (PMID: 24319099). ClinVar contains an entry for this variant (Variation ID: 212021). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt 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. |