NM_015909.4(NBAS):c.2950del (p.Ile984fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 23, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000596241.5

Allele description [Variation Report for NM_015909.4(NBAS):c.2950del (p.Ile984fs)]

NM_015909.4(NBAS):c.2950del (p.Ile984fs)

Gene:
NBAS:NBAS subunit of NRZ tethering complex [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p24.3
Genomic location:
Preferred name:
NM_015909.4(NBAS):c.2950del (p.Ile984fs)
HGVS:
  • NC_000002.12:g.15402294del
  • NG_032964.1:g.164060del
  • NM_015909.4:c.2950delMANE SELECT
  • NP_056993.2:p.Ile984fs
  • NC_000002.11:g.15542413delT
  • NC_000002.11:g.15542418del
  • NM_015909.3:c.2950delA
  • NR_052013.3:n.2980del
  • p.Ile984LeufsX8
Protein change:
I984fs
Links:
dbSNP: rs776797592
NCBI 1000 Genomes Browser:
rs776797592
Molecular consequence:
  • NM_015909.4:c.2950del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_052013.3:n.2980del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000707635EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Likely pathogenic
(Apr 26, 2017)
germlineclinical testing

Citation Link,

SCV001168056GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 20, 2018)
germlineclinical testing

Citation Link,

SCV001235901Invitaecriteria provided, single submitter
Pathogenic
(Feb 8, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001447378Institute of Medical Genetics and Applied Genomics, University Hospital Tübingencriteria provided, single submitter
Pathogenic
(Oct 23, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot provided1not providedclinical testing

Citations

PubMed

Biallelic Mutations in NBAS Cause Recurrent Acute Liver Failure with Onset in Infancy.

Haack TB, Staufner C, Köpke MG, Straub BK, Kölker S, Thiel C, Freisinger P, Baric I, McKiernan PJ, Dikow N, Harting I, Beisse F, Burgard P, Kotzaeridou U, Kühr J, Himbert U, Taylor RW, Distelmaier F, Vockley J, Ghaloul-Gonzalez L, Zschocke J, Kremer LS, et al.

Am J Hum Genet. 2015 Jul 2;97(1):163-9. doi: 10.1016/j.ajhg.2015.05.009. Epub 2015 Jun 11.

PubMed [citation]
PMID:
26073778
PMCID:
PMC4572578

Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts.

Staufner C, Haack TB, Köpke MG, Straub BK, Kölker S, Thiel C, Freisinger P, Baric I, McKiernan PJ, Dikow N, Harting I, Beisse F, Burgard P, Kotzaeridou U, Lenz D, Kühr J, Himbert U, Taylor RW, Distelmaier F, Vockley J, Ghaloul-Gonzalez L, Ozolek JA, et al.

J Inherit Metab Dis. 2016 Jan;39(1):3-16. doi: 10.1007/s10545-015-9896-7. Epub 2015 Nov 5.

PubMed [citation]
PMID:
26541327
See all PubMed Citations (4)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000707635.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV001168056.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001235901.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447378.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

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