ClinVar Miner

Submissions for variant NM_015909.4(NBAS):c.2950del (p.Ile984fs) (rs776797592)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000596241 SCV000707635 likely pathogenic not provided 2017-04-26 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000602655 SCV000712173 pathogenic Infantile liver failure 2017-09-01 criteria provided, single submitter clinical testing The p.Ile984LeufsX8 variant in NBAS has not been reported in individuals with di sease and has been identified in 9/120,878 of chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs140841721). Althou gh this variant has been seen in the general population, its frequency is low en ough to be consistent with a recessive carrier frequency. This variant is predic ted to cause a frameshift, which alters the protein?s amino acid sequence beginn ing at position 984 and leads to a premature termination codon 8 amino acids dow nstream. This alteration is then predicted to lead to a truncated or absent prot ein. Homozygous or compound heterozygous mutations in NBAS have been associated with Infantile liver failure syndrome 2. In summary, this variant meets our cr iteria to be classified as pathogenic for Infantile liver failure syndrome 2 in an autosomal recessive manner based on low frequency in controls and functional prediction
GeneDx RCV000596241 SCV001168056 likely pathogenic not provided 2018-12-20 criteria provided, single submitter clinical testing The c.2950delA variant in the NBAS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.2950delA variant causes a frameshift starting with codon Isoleucine 984, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Ile984LeufsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.2950delA variant is observed in 32/126374 (0.025%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016). We interpret c.2950delA as a likely pathogenic variant.
Invitae RCV000596241 SCV001235901 pathogenic not provided 2019-02-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile984Leufs*8) in the NBAS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776797592, ExAC 0.01%). This variant has not been reported in the literature in individuals with NBAS-related disease. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000596241 SCV001447378 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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