NM_000263.4(NAGLU):c.2116C>T (p.Gln706Ter) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Jan 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001060496.2

Allele description [Variation Report for NM_000263.4(NAGLU):c.2116C>T (p.Gln706Ter)]

NM_000263.4(NAGLU):c.2116C>T (p.Gln706Ter)

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.2116C>T (p.Gln706Ter)
HGVS:
  • NC_000017.11:g.42544122C>T
  • NG_011552.1:g.13190C>T
  • NM_000263.4:c.2116C>TMANE SELECT
  • NP_000254.2:p.Gln706Ter
  • NC_000017.10:g.40696140C>T
  • NM_000263.3:c.2116C>T
Protein change:
Q706*
Links:
dbSNP: rs752527478
NCBI 1000 Genomes Browser:
rs752527478
Molecular consequence:
  • NM_000263.4:c.2116C>T - nonsense - [Sequence Ontology: SO:0001587]

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 (CMT2V)
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2V; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2V
Identifiers:
MONDO: MONDO:0014665; MedGen: C4225306; Orphanet: 447964; OMIM: 616491

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001225189Invitaecriteria provided, single submitter
Likely pathogenic
(Jan 15, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001225189.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change results in a premature translational stop signal in the NAGLU gene (p.Gln706*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acids of the NAGLU protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Sanfilippo syndrome type B (PMID: 9443875). ClinVar contains an entry for this variant (Variation ID: 553260). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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

Last Updated: Jun 14, 2021

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