NM_000263.4(NAGLU):c.2116C>T (p.Gln706Ter) AND Mucopolysaccharidosis, MPS-III-B

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 2, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000668667.2

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000793305Counsylcriteria provided, single submitter
Likely pathogenic
(Aug 10, 2017)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001448365Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Nov 2, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular genetics of mucopolysaccharidosis type IIIA and IIIB: Diagnostic, clinical, and biological implications.

Yogalingam G, Hopwood JJ.

Hum Mutat. 2001 Oct;18(4):264-81. Review.

PubMed [citation]
PMID:
11668611

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
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000793305.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001448365.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: NAGLU c.2116C>T (p.Gln706X) results in a premature termination codon in the last exon (exon 6) of the NAGLU gene and predicted to cause a truncation of the encoded protein. The variant allele was found at a frequency of 8e-06 in 251326 control chromosomes. c.2116C>T has been reported in the literature in individuals affected with Mucopolysaccharidosis Type IIIB (Sanfilippo Syndrome B) and subsequently cited by others (example, Zhao_1998, Whitley_2018, Schmidtchen_1998, Yogalingam_2001, Jain_2018). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal NAGLU enzyme activity and elevated urine glycosaminoglycan (GAG) and cerebrospinal fluid heparan sulfate levels (example, Whitley_2018). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic citing at-least one overlapping publication utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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