ClinVar Miner

Submissions for variant NM_006432.4(NPC2):c.352G>T (p.Glu118Ter) (rs80358266)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000009001 SCV000797205 pathogenic Niemann-Pick disease, type C2 2018-01-16 criteria provided, single submitter clinical testing
Invitae RCV000009001 SCV001236045 pathogenic Niemann-Pick disease, type C2 2020-09-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu118*) in the NPC2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358266, ExAC 0.003%). This variant has been observed in individuals affected with Niemann-Pick disease type C (PMID: 11567215, 25772320, 28808920). ClinVar contains an entry for this variant (Variation ID: 8480). Loss-of-function variants in NPC2 are known to be pathogenic (PMID: 25145893). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193596 SCV001362526 pathogenic Niemann-Pick disease, type C 2020-12-04 criteria provided, single submitter clinical testing Variant summary: NPC2 c.352G>T (p.Glu118X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251482 control chromosomes (gnomAD). c.352G>T has been reported in the literature in multiple individuals affected with Niemann-Pick Disease Type C (e.g. Millat_2001, Topcu_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000009001 SCV000029215 pathogenic Niemann-Pick disease, type C2 2001-11-01 no assertion criteria provided literature only
GeneReviews RCV000009001 SCV000041173 pathologic Niemann-Pick disease, type C2 2008-07-22 no assertion criteria provided curation Converted during submission to Pathogenic.
Natera, Inc. RCV000009001 SCV001464115 pathogenic Niemann-Pick disease, type C2 2020-09-16 no assertion criteria provided clinical testing

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