Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002829599 | SCV003217639 | pathogenic | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with NBAS-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Val1613Aspfs*4) in the NBAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226556 | SCV003923098 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2023-03-21 | criteria provided, single submitter | clinical testing | Variant summary: NBAS c.4838_4839delTG (p.Val1613AspfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic in ClinVar and reported in association with NBAS-related disease in HGMD. The variant allele was found at a frequency of 4e-06 in 251392 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.4838_4839delTG in individuals affected with Liver Failure Acute Infantile, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |