Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001806835 | SCV002051394 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2021-12-27 | criteria provided, single submitter | clinical testing | Variant summary: NBAS c.6909T>A (p.Cys2303X) results in a premature termination codon in exon 52 (i.e. in the last exon), predicted to cause a truncation of the encoded protein, but is not expected to result in nonsense mediated decay (NMD). The variant allele was found at a frequency of 4e-06 in 251446 control chromosomes (gnomAD). To our knowledge, no occurrence of c.6909T>A in individuals affected with Liver Failure Acute Infantile, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. However, a truncating variant downstream from this position (c.6966_6969delAGGGinsTC (p.Gln2322Hisfs*18)) has been reported in the literature in a compound heterozygous individual affected with NBAS-associated disease, with clinical symptoms including optic atrophy, motor delay, hypogammaglobulinemia and elevated liver transaminases (PMID: 31761904). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV001885260 | SCV002156989 | uncertain significance | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys2303*) in the NBAS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 69 amino acid(s) of the NBAS protein. This variant is present in population databases (rs778338208, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NBAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1331491). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |