Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002037573 | SCV002109723 | uncertain significance | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with OBSL1-related conditions. This variant is present in population databases (rs757802630, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Cys1153*) in the OBSL1 gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004699491 | SCV005203806 | pathogenic | 3M syndrome 2 | 2024-07-02 | criteria provided, single submitter | clinical testing | Variant summary: OBSL1 c.3459_3460delTG (p.Cys1153X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.2e-05 in 243460 control chromosomes, predominantly at a frequency of 1.8e-05 within the Non-Finnish European subpopulation in the gnomAD database. To our knowledge, no occurrence of c.3459_3460delTG in individuals affected with Three M Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1345817). Based on the evidence outlined above, the variant was classified as pathogenic. |