Total submissions: 15
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Medical Genetics, |
RCV000023096 | SCV001451936 | pathogenic | Osteodysplastic primordial dwarfism, type 1 | criteria provided, single submitter | research | ||
| Beijing Key Laboratry for Genetics of Birth Defects, |
RCV000202312 | SCV001739477 | likely pathogenic | Roifman syndrome | 2020-02-28 | criteria provided, single submitter | clinical testing | |
| Blueprint Genetics | RCV001596939 | SCV001832417 | pathogenic | not provided | 2019-11-30 | criteria provided, single submitter | clinical testing | |
| Genetic Services Laboratory, |
RCV001596939 | SCV002070508 | pathogenic | not provided | 2021-06-25 | criteria provided, single submitter | clinical testing | The non-coding variant, n.51G>A, has been described in gnomAD with an allele frequency of 0.054% in the South Asian sub-population (dbSNP rsrs181195449). This sequence change is located in the 5' stem loop critical region. The n.51G>A is a known pathogenic sequence change and has been reported in multiple cases with microcephalic osteodysplastic primordial dwarfism either in the homozygous or compound heterozygous state (PMIDs: 21474760, 23794361, 32628740, 29265708, 27312855, 26522830). Functional studies have also demonstrated that this sequence change reduced U12-dependent splicing activity by 90% compared to wildtype (PMID:21474760). Based on this information this variant is being classified as pathogenic. |
| Labcorp Genetics |
RCV001596939 | SCV002243422 | pathogenic | not provided | 2024-01-04 | 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 (rs188343279, gnomAD 0.07%). This variant has been observed in individual(s) with RNU4ATAC-related conditions (PMID: 21474760, 26522830). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30178). Functional studies have shown that this variant disrupts ncRNA function (PMID: 21474760). This variant is located within the 5' stem-loop region of the RNU4ATAC RNA, which includes the 15.5K binding site and is important for spliceosome assembly (PMID: 32628740). A significant number of disease-associated RNU4ATAC variants are found in this region (PMID: 32628740, 30368667). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002482901 | SCV002793874 | pathogenic | Osteodysplastic primordial dwarfism, type 1; Lowry-Wood syndrome; Roifman syndrome | 2022-02-27 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001596939 | SCV002822684 | pathogenic | not provided | 2024-08-01 | criteria provided, single submitter | clinical testing | RNU4ATAC: PM3:Very Strong, PS3:Moderate, PM2:Supporting |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000202312 | SCV003934281 | pathogenic | Roifman syndrome | 2023-05-09 | criteria provided, single submitter | clinical testing | Variant summary: RNU4ATAC n.51G>A alters a nucleotide in the non-coding RNA. The variant allele was found at a frequency of 0.00043 in 130510 control chromosomes. n.51G>A has been reported in the literature in multiple individuals affected with Microcephalic osteodysplastic primordial dwarfism, type I or Roifman Syndrome. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (He_2012). The following publications have been ascertained in the context of this evaluation (PMID: 21474760, 26522830). Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute for Clinical Genetics, |
RCV001596939 | SCV004026349 | pathogenic | not provided | 2023-04-19 | criteria provided, single submitter | clinical testing | PS4_MOD, PP1, PS3, PM3 |
| Prevention |
RCV003415730 | SCV004115105 | pathogenic | RNU4ATAC-related disorder | 2022-09-26 | criteria provided, single submitter | clinical testing | The RNU4ATAC n.51G>A is a noncoding alteration. This variant has been reported in the homozygous and compound heterozygous states in multiple individuals with RNU4ATAC-related disorders, and functional studies support its pathogenicity (He et al. 2011. PubMed ID: 21474760; Abdel-Salam et al. 2013. PubMed ID: 23794361; Merico et al. 2015. PubMed ID: 26522830; Farach et al. 2017. PubMed ID: 29265708; Benoit-Pilven et al. 2020. PubMed ID: 32628740). This variant is reported in 0.063% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-122288506-G-A). This variant is interpreted as pathogenic. |
| Institute of Medical Genetics and Applied Genomics, |
RCV000023096 | SCV005400655 | pathogenic | Osteodysplastic primordial dwarfism, type 1 | 2024-11-19 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000023096 | SCV000044387 | pathogenic | Osteodysplastic primordial dwarfism, type 1 | 2015-11-02 | no assertion criteria provided | literature only | |
| OMIM | RCV000202312 | SCV000257312 | pathogenic | Roifman syndrome | 2015-11-02 | no assertion criteria provided | literature only | |
| OMIM | RCV001255662 | SCV001432227 | pathogenic | Lowry-Wood syndrome | 2015-11-02 | no assertion criteria provided | literature only | |
| Service de Génétique Moléculaire, |
RCV000023096 | SCV001432350 | pathogenic | Osteodysplastic primordial dwarfism, type 1 | no assertion criteria provided | clinical testing |