NM_006432.4(NPC2):c.436C>T (p.Gln146Ter) AND Niemann-Pick disease, type C2

Clinical significance:Likely pathogenic (Last evaluated: Aug 3, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000009006.3

Allele description [Variation Report for NM_006432.4(NPC2):c.436C>T (p.Gln146Ter)]

NM_006432.4(NPC2):c.436C>T (p.Gln146Ter)

Gene:
NPC2:NPC intracellular cholesterol transporter 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.3
Genomic location:
Preferred name:
NM_006432.4(NPC2):c.436C>T (p.Gln146Ter)
HGVS:
  • NC_000014.9:g.74480707G>A
  • NG_007117.1:g.17675C>T
  • NM_001363688.1:c.436C>T
  • NM_006432.4:c.436C>T
  • NP_001350617.1:p.Gln146Ter
  • NP_006423.1:p.Gln146Ter
  • NC_000014.8:g.74947410G>A
  • NM_006432.3:c.436C>T
Protein change:
Q146*; GLN146TER
Links:
OMIM: 601015.0009; dbSNP: rs104894457
NCBI 1000 Genomes Browser:
rs104894457
Molecular consequence:
  • NM_001363688.1:c.436C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006432.4:c.436C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Niemann-Pick disease, type C2 (NPC2)
Identifiers:
MONDO: MONDO:0011873; MedGen: C1843366; Orphanet: 646; OMIM: 607625

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000029220OMIMno assertion criteria providedPathogenic
(Apr 1, 2007)
germlineliterature only

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

SCV000793043Counsylcriteria provided, single submitter
Likely pathogenic
(Aug 3, 2017)
unknownclinical testing

PubMed (3)
[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 providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Niemann-Pick C disease: functional characterization of three NPC2 mutations and clinical and molecular update on patients with NPC2.

Verot L, Chikh K, Freydière E, Honoré R, Vanier MT, Millat G.

Clin Genet. 2007 Apr;71(4):320-30.

PubMed [citation]
PMID:
17470133

Niemann-Pick Type C-2 Disease: Identification by Analysis of Plasma Cholestane-3β,5α,6β-Triol and Further Insight into the Clinical Phenotype.

Reunert J, Lotz-Havla AS, Polo G, Kannenberg F, Fobker M, Griese M, Mengel E, Muntau AC, Schnabel P, Sommerburg O, Borggraefe I, Dardis A, Burlina AP, Mall MA, Ciana G, Bembi B, Burlina AB, Marquardt T.

JIMD Rep. 2015;23:17-26. doi: 10.1007/8904_2015_423. Epub 2015 Mar 13.

PubMed [citation]
PMID:
25772320
PMCID:
PMC4484906
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000029220.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an Algerian male infant with NPC2 (607625), Verot et al. (2007) identified a homozygous mutation in the NPC2 gene, resulting in a gln146-to-ter (Q146X) substitution. Although this mutation could have theoretically resulted in a protein lacking only the last 6 residues, Western blot analysis and immunofluorescent studies showed no detectable protein. However, RT-PCR studies showed normal levels of mRNA, which excluded nonsense-mediated decay. Verot et al. (2007) concluded that the mutant protein must be unstable. The patient had neonatal cholestatic icterus and hepatosplenomegaly with ascites, from which he recovered, and was alive at 9 months of age with no neurologic signs.

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

From Counsyl, SCV000793043.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2021

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