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NM_000271.5(NPC1):c.2972_2973del (p.Gln991fs) AND NPC1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 19, 2023
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:
RCV003416051.4

Allele description [Variation Report for NM_000271.5(NPC1):c.2972_2973del (p.Gln991fs)]

NM_000271.5(NPC1):c.2972_2973del (p.Gln991fs)

Gene:
NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
18q11.2
Genomic location:
Preferred name:
NM_000271.5(NPC1):c.2972_2973del (p.Gln991fs)
HGVS:
  • NC_000018.10:g.23538610_23538611del
  • NG_012795.1:g.53007_53008del
  • NM_000271.5:c.2972_2973delMANE SELECT
  • NP_000262.2:p.Gln991fs
  • NC_000018.9:g.21118574_21118575del
  • NC_000018.9:g.21118574_21118575delCT
  • NM_000271.4:c.2972_2973del
  • NM_000271.4:c.2972_2973delAG
Protein change:
Q991fs
Links:
dbSNP: rs756815030
NCBI 1000 Genomes Browser:
rs756815030
Molecular consequence:
  • NM_000271.5:c.2972_2973del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
NPC1-related disorder
Synonyms:
NPC1-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004118429PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 19, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004118429.1

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

Description

The NPC1 c.2972_2973delAG variant is predicted to result in a frameshift and premature protein termination (p.Gln991Argfs*15). This variant has been reported in individuals with Niemann-Pick type C (Tarugi et al. 2002. PubMed ID: 12401890; Millat et al. 2005. PubMed ID: 16126423; Schicks et al. 2013. PubMed ID: 23427322; Zhang et al. 2014. PubMed ID: 24915861; Imrie et al. 2015. PubMed ID: 26666848). This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-21118573-CCT-C). Frameshift variants in NPC1 are expected to be pathogenic. This variant is interpreted as pathogenic.

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

Last Updated: Oct 20, 2024