Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV002244201 | SCV002512568 | uncertain significance | Infantile liver failure syndrome 2 | 2021-06-28 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderate |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700696 | SCV005205380 | uncertain significance | not specified | 2024-06-03 | criteria provided, single submitter | clinical testing | Variant summary: NBAS c.5465_5467delinsCTT (p.Asn1822_Ile1823delinsThrPhe) results in an in-frame deletion-insertion that is predicted to cause changes in two amino acids. The variant allele was found at a frequency of 0.00083 in 125487 control chromosomes in the gnomAD database, including 1 homozygote (gnomAD Variant Co-Occurrence dataset, v2.1.1). This frequency is not significantly higher than estimated for a pathogenic variant in NBAS causing Liver Failure Acute Infantile, Type 2 (0.00083 vs 0.0011), allowing no conclusion about variant significance. Both of the constituent SNVs that make up this variant, c.5465A>C (p.Asn1822Thr) and c.5467A>T (p.Ile1823Phe), have been reported in the literature in individuals affected with Liver Failure Acute Infantile, Type 2 (e.g., Nazmi_NBAS_LI_2021). However, this report did not provide convincing conclusions about association of the variant with Liver Failure Acute Infantile, Type 2, and it is unclear if the two homozygous SNVs occurred in the same individual. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 34396667). ClinVar contains an entry for this variant (Variation ID: 1683680). Based on the evidence outlined above, the variant was classified as uncertain significance. |