Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV001090145 | SCV001245591 | likely pathogenic | Roifman syndrome | 2019-10-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002555934 | SCV003524680 | likely pathogenic | not provided | 2023-01-18 | criteria provided, single submitter | clinical testing | This variant occurs in the RNU4ATAC gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has been observed in individual(s) with Roifman syndrome (PMID: 29263834; external communication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 870579). This variant is located within the Sm protein-binding region of the RNU4ATAC RNA, which is important for small nuclear RNA maturation (PMID: 32628740). A significant number of disease-associated RNU4ATAC variants are found in this region (PMID: 32628740, 30368667). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Prevention |
RCV003396739 | SCV004119337 | likely pathogenic | RNU4ATAC-related disorder | 2022-12-08 | criteria provided, single submitter | clinical testing | The RNU4ATAC n.116A>G is a noncoding alteration. This variant in the compound heterozygous condition was reported in at least two individuals with Roifman syndrome (Figure 5, Schejter et al 2017. PubMed ID: 29263834; Table 1, Benoit-Pilven et al 2020. PubMed ID: 32628740; Hallermayr et al. 2018. PubMed ID: 30455926). This variant is reported in 0.0061% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-122288571-A-G). Different variants affecting the same nucleotide (n.116A>T and n.116A>C) were also reported to be pathogenic (Table 1, Benoit-Pilven et al 2020. PubMed ID: 32628740). This variant is interpreted as likely pathogenic. |