Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001550908 | SCV001771310 | likely pathogenic | not provided | 2019-02-13 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001550908 | SCV002937967 | uncertain significance | not provided | 2022-02-24 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs752897486, gnomAD 0.003%). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1190268). This variant has not been reported in the literature in individuals affected with ASNS-related conditions. This variant, c.753_755del, results in the deletion of 1 amino acid(s) of the ASNS protein (p.Arg252del), but otherwise preserves the integrity of the reading frame. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226478 | SCV003923280 | uncertain significance | not specified | 2023-03-23 | criteria provided, single submitter | clinical testing | Variant summary: ASNS c.753_755delAAG (p.Arg252del) results in an in-frame deletion that is predicted to remove 1 amino acid within the Asparagine synthase domain (IPR001962) of the encoded protein. The variant allele was found at a frequency of 8e-06 in 249586 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.753_755delAAG in individuals affected with Asparagine Synthetase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. One laboratory classified the variant as likely pathogenic, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |