Submissions for variant NM_006432.5(NPC2):c.332del (p.Asn111fs)

dbSNP: rs80358265

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000020647	SCV000388521	uncertain significance	Niemann-Pick disease, type C2	2017-04-27	criteria provided, single submitter	clinical testing	The NPC2 c.332delA (p.Asn111IlefsTer5) variant results in a frameshift and is predicted to result in premature termination of the protein. The variant has been reported in one study and was found in a single patient with Niemann-Pick disease type C (NPC2)who was compound heterozygous for the p.Asn111IlefsTer5 variant and a second stop-gained variant (Naureckiene et al. 2000). The variant was also shown to be absent from eight other individuals who represented unaffected controls, patients with NPC1, or patients with other diseases but is reported at a frequency of 0.000921 in the Other population of the Genome Aggregation Database, although this is based on one allele only in a region of good sequence coverage so the variant is assumed to be rare. Based on the evidence and potential impact of frameshift variants, the p.Asn111IlefsTer5 is classified as of uncertain clinical significance but suspicious for pathogenicity for Niemann-Pick disease type C. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM	RCV000020647	SCV000029213	pathogenic	Niemann-Pick disease, type C2	2000-12-22	no assertion criteria provided	literature only
GeneReviews	RCV000020647	SCV000041172	not provided	Niemann-Pick disease, type C2		no assertion provided	literature only