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NM_006432.5(NPC2):c.441+1G>A AND NPC2-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 19, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV003935083.2

Allele description [Variation Report for NM_006432.5(NPC2):c.441+1G>A]

NM_006432.5(NPC2):c.441+1G>A

Genes:
ACYP1:acylphosphatase 1 [Gene - OMIM - HGNC]
NPC2:NPC intracellular cholesterol transporter 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q24.3
Genomic location:
Preferred name:
NM_006432.5(NPC2):c.441+1G>A
Other names:
UNC
HGVS:
  • NC_000014.9:g.74480701C>T
  • NG_007117.1:g.17681G>A
  • NM_001363688.1:c.442G>A
  • NM_001375440.1:c.364-413G>A
  • NM_006432.5:c.441+1G>AMANE SELECT
  • NP_001350617.1:p.Val148Ile
  • NC_000014.8:g.74947404C>T
  • NM_006432.3:c.441+1G>A
  • NM_006432.4:c.441+1G>A
Protein change:
V148I
Links:
dbSNP: rs140130028
NCBI 1000 Genomes Browser:
rs140130028
Molecular consequence:
  • NM_001375440.1:c.364-413G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001363688.1:c.442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006432.5:c.441+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
NPC2-related disorder
Synonyms:
NPC2-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004747967PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Uncertain significance
(Aug 19, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004747967.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The NPC2 c.441+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was detected in the heterozygous state in one patient with a possible Niemann-Pick disease Type C phenotype and with no other pathogenic or likely pathogenic variants (Bauer et al. 2013. PubMed ID: 23773996). Another study reported this variant in the heterozygous state in patients with two autosomal dominant disorders (Parkinson's disease and frontotemporal lobar degeneration), and also in one control individual (Zech et al. 2013. PubMed ID: 24386122). At PreventionGenetics, we previously detected this variant in the heterozygous state in several other patients with various Niemann-Pick phenotypes. However, this variant is reported in 0.65% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including three homozygotes, which might be too common to be a highly penetrant cause of disease. While we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Oct 13, 2024