NM_000263.4(NAGLU):c.2T>C (p.Met1Thr) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 10, 2023
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:: RCV003767964.2

Allele description [Variation Report for NM_000263.4(NAGLU):c.2T>C (p.Met1Thr)]

NM_000263.4(NAGLU):c.2T>C (p.Met1Thr)

Genes:

LOC130060903:ATAC-STARR-seq lymphoblastoid silent region 8533 [Gene]
NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_000263.4(NAGLU):c.2T>C (p.Met1Thr)

HGVS:

NC_000017.11:g.42536274T>C
NG_011552.1:g.5342T>C
NM_000263.4:c.2T>CMANE SELECT
NP_000254.2:p.Met1Thr
NC_000017.10:g.40688292T>C
NM_000263.3:c.2T>C

Protein change:

M1T

Links:

dbSNP: rs1013345784

NCBI 1000 Genomes Browser:

rs1013345784

Molecular consequence:

NM_000263.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_000263.4:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004579384	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 10, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9950362, 18218046, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004579384

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 10, 2023)

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

Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha-N-acetylglucosaminidase gene mutations.

Bunge S, Knigge A, Steglich C, Kleijer WJ, van Diggelen OP, Beck M, Gal A.

J Med Genet. 1999 Jan;36(1):28-31.

PubMed [citation]

PMID:: 9950362
PMCID:: PMC1762943

Molecular analysis of mucopolysaccharidosis type IIIB in Portugal: evidence of a single origin for a common mutation (R234C) in the Iberian Peninsula.

Mangas M, Nogueira C, Prata MJ, Lacerda L, Coll MJ, Soares G, Ribeiro G, Amaral O, Ferreira C, Alves C, Coutinho MF, Alves S.

Clin Genet. 2008 Mar;73(3):251-6. doi: 10.1111/j.1399-0004.2007.00951.x. Epub 2008 Jan 23.

PubMed [citation]

PMID:: 18218046

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004579384.1

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

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 553224). Disruption of the initiator codon has been observed in individual(s) with mucopolysaccharidosis type III (PMID: 9950362, 18218046). This sequence change affects the initiator methionine of the NAGLU mRNA. The next in-frame methionine is located at codon 157.

#	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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