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

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Jan 29, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000596241.17

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_000002.11:g.15542413del
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.15542413del
NC_000002.11:g.15542413delT
NC_000002.11:g.15542418del
NM_015909.3:c.2950del
NM_015909.3:c.2950delA
NM_015909.4:c.2950delAMANE SELECT
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:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000707635	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely pathogenic (Apr 26, 2017)	germline	clinical testing	Citation Link,
SCV001168056	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Aug 29, 2023)	germline	clinical testing	Citation Link,
SCV001235901	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 29, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26073778, 26541327, 27789416, 28031453, 31761904, 28492532
SCV001447378	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004138624	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Dec 1, 2022)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical 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 (7)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000707635.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneDx, SCV001168056.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30609409, 31589614, 31980526, 31964843, 34386911, 31015584, 31761904)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001235901.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

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. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453). This variant is present in population databases (rs776797592, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with NBAS-related disorders (PMID: 31761904). ClinVar contains an entry for this variant (Variation ID: 501319). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004138624.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

NBAS: PVS1, PM2:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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