NM_015909.4(NBAS):c.6433-2A>G AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 23, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002570461.4

Allele description [Variation Report for NM_015909.4(NBAS):c.6433-2A>G]

NM_015909.4(NBAS):c.6433-2A>G

Gene:

NBAS:NBAS subunit of NRZ tethering complex [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p24.3

Genomic location:

Preferred name:

NM_015909.4(NBAS):c.6433-2A>G

HGVS:

NC_000002.12:g.15190405T>C
NG_032964.1:g.375944A>G
NG_032964.2:g.375929A>G
NM_015909.4:c.6433-2A>GMANE SELECT
NC_000002.11:g.15330529T>C
NC_000002.11:g.15330529T>C
NM_015909.4:c.[6433-2A>G]MANE SELECT
NM_015909.4:c.[6433-2A>G]

Links:

dbSNP: rs200365734

NCBI 1000 Genomes Browser:

rs200365734

Molecular consequence:

NM_015909.4:c.6433-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV003011130	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 23, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 32805445, 16199547, 26073778, 26541327, 27789416, 28031453, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003011130

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 23, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A 34-year-old Japanese patient exhibiting NBAS deficiency with a novel mutation and extended phenotypic variation.

Suzuki S, Kokumai T, Furuya A, Nagamori T, Matsuo K, Ueda O, Mukai T, Ito Y, Yano K, Fujieda K, Okuno A, Tanahashi Y, Azuma H.

Eur J Med Genet. 2020 Nov;63(11):104039. doi: 10.1016/j.ejmg.2020.104039. Epub 2020 Aug 14.

PubMed [citation]

PMID:: 32805445

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003011130.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 32805445). ClinVar contains an entry for this variant (Variation ID: 975151). Disruption of this splice site has been observed in individual(s) with NBAS deficiency (PMID: 32805445). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 48 of the NBAS gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453).

#	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

Last Updated: Sep 29, 2024

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