NM_006432.3(NPC2):c.58G>T (p.Glu20Ter) AND Niemann-Pick disease type C2

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Mar 31, 2017
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:: RCV000008998.2

Allele description

NM_006432.3(NPC2):c.58G>T (p.Glu20Ter)

Gene:

NPC2:NPC intracellular cholesterol transporter 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_006432.3(NPC2):c.58G>T (p.Glu20Ter)

HGVS:

NC_000014.9:g.74493217C>A
NG_007117.1:g.5165G>T
NM_006432.3:c.58G>T
NP_006423.1:p.Glu20Ter
NC_000014.8:g.74959920C>A

Protein change:

E20*; GLU20TER

Links:

OMIM: 601015.0001; dbSNP: rs80358260

NCBI 1000 Genomes Browser:

rs80358260

Molecular consequence:

NM_006432.3:c.58G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000029212	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2007)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 11125141, 11567215, 17470133
SCV000041174	GeneReviews	no assertion criteria provided	pathologic (Jul 22, 2008)	not provided	curation
SCV000790656	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (Mar 31, 2017)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22073306, 15937921, 21084287, 11567215, 11333381, 16757520, 11125141, 12955717 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000029212

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2007)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000041174

GeneReviews

no assertion criteria provided

pathologic
(Jul 22, 2008)

not provided

curation

SCV000790656

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Pathogenic
(Mar 31, 2017)

unknown

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not provided	not provided	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Protein replacement therapy partially corrects the cholesterol-storage phenotype in a mouse model of Niemann-Pick type C2 disease.

Nielsen GK, Dagnaes-Hansen F, Holm IE, Meaney S, Symula D, Andersen NT, Heegaard CW.

PLoS One. 2011;6(11):e27287. doi: 10.1371/journal.pone.0027287. Epub 2011 Nov 3.

PubMed [citation]

PMID:: 22073306
PMCID:: PMC3207855

See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000029212.1

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

Description

Naureckiene et al. (2000) identified a patient with NPC2 (607625) who was homozygous for a G-to-T transversion in exon 1 of the HE1 gene, resulting in a glu20-to-ter substitution.

Millat et al. (2001) stated that they found that the E20X mutation had an overall allele frequency of 56% in a study of 8 families with NPC2 from widely separated geographic areas. Homozygosity was associated with a severe rapid disease course. Pronounced lung involvement leading to death from respiratory failure occurred in some patients.

Verot et al. (2007) reported 2 unrelated patients with NPC2 who were homozygous for the E20X mutation. They had a severe phenotype, with early death at ages 15 months and 3.5 years, respectively.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneReviews, SCV000041174.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

Converted during submission to Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	not provided	not provided	Assert pathogenicity		not provided	not provided	not provided	not provided

From Counsyl, SCV000790656.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 24, 2019

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