NM_000263.4(NAGLU):c.1773del (p.Leu591_Leu592insTer) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 21, 2021
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:: RCV001888331.4

Allele description [Variation Report for NM_000263.4(NAGLU):c.1773del (p.Leu591_Leu592insTer)]

NM_000263.4(NAGLU):c.1773del (p.Leu591_Leu592insTer)

Gene:

NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_000263.4(NAGLU):c.1773del (p.Leu591_Leu592insTer)

HGVS:

NC_000017.11:g.42543779del
NG_011552.1:g.12847del
NM_000263.4:c.1773delMANE SELECT
NP_000254.2:p.Leu591_Leu592insTer
NC_000017.10:g.40695797del

Links:

dbSNP: rs2143113566

NCBI 1000 Genomes Browser:

rs2143113566

Molecular consequence:

NM_000263.4:c.1773del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Mucopolysaccharidosis, MPS-III-B (MPS3B)
Synonyms:: NAGLU DEFICIENCY; Mucopoly-saccharidosis type 3B; Sanfilippo syndrome B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009656; MedGen: C0086648; OMIM: 252920

Name:: Charcot-Marie-Tooth disease axonal type 2V
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:: MONDO: MONDO:0014665; MedGen: C5569050; Orphanet: 447964; OMIM: 616491

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Mus musculus SPT4A, DSIF elongation factor subunit (Supt4a), transcript variant ...
Mus musculus SPT4A, DSIF elongation factor subunit (Supt4a), transcript variant 2, mRNA
gi|1246764174|ref|NM_001355753.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002143001	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 21, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9443875, 29661560, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002143001

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 21, 2021)

germline

clinical testing

PubMed (3)
[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

Genotype-phenotype correspondence in Sanfilippo syndrome type B.

Zhao HG, Aronovich EL, Whitley CB.

Am J Hum Genet. 1998 Jan;62(1):53-63.

PubMed [citation]

PMID:: 9443875
PMCID:: PMC1376807

Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B.

Whitley CB, Cleary M, Eugen Mengel K, Harmatz P, Shapiro E, Nestrasil I, Haslett P, Whiteman D, Alexanderian D.

J Pediatr. 2018 Jun;197:198-206.e2. doi: 10.1016/j.jpeds.2018.01.044. Epub 2018 Apr 13.

PubMed [citation]

PMID:: 29661560

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002143001.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu592*) in the NAGLU gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 152 amino acid(s) of the NAGLU protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NAGLU protein in which other variant(s) (p.Gln706*) have been determined to be pathogenic (PMID: 9443875, 29661560). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with NAGLU-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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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