ClinVar Miner

Submissions for variant NM_006432.5(NPC2):c.58G>T (p.Glu20Ter)

dbSNP: rs80358260
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586093 SCV000698700 pathogenic Niemann-Pick disease, type C 2017-06-26 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000008998 SCV000894036 pathogenic Niemann-Pick disease, type C2 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000008998 SCV001211647 pathogenic Niemann-Pick disease, type C2 2025-01-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu20*) in the NPC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC2 are known to be pathogenic (PMID: 25145893). This variant is present in population databases (rs80358260, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Niemann-Pick disease type C (PMID: 11125141, 26666848). ClinVar contains an entry for this variant (Variation ID: 8477). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000008998 SCV001525184 pathogenic Niemann-Pick disease, type C2 2020-01-31 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000008998 SCV002512491 pathogenic Niemann-Pick disease, type C2 2022-01-28 criteria provided, single submitter clinical testing ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PM2 moderate, PM3 very strong
Revvity Omics, Revvity RCV000008998 SCV003824143 pathogenic Niemann-Pick disease, type C2 2022-06-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV004018603 SCV004990701 pathogenic Inborn genetic diseases 2022-05-23 criteria provided, single submitter clinical testing The c.58G>T (p.E20*) alteration, located in exon 1 (coding exon 1) of the NPC2 gene, consists of a G to T substitution at nucleotide position 58. This changes the amino acid from a glutamic acid (E) to a stop codon at amino acid position 20. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This alteration has been detected in the homozygous state, and in conjunction with another NPC2 disease-causing alteration, in multiple individuals with Niemann-Pick disease, type C2 (Millat, 2001; Park, 2003; Imrie, 2015; Sudrié-Arnaud, 2021). Based on the available evidence, this alteration is classified as pathogenic.
OMIM RCV000008998 SCV000029212 pathogenic Niemann-Pick disease, type C2 2007-04-01 no assertion criteria provided literature only
GeneReviews RCV000008998 SCV000041174 not provided Niemann-Pick disease, type C2 no assertion provided literature only
Counsyl RCV000008998 SCV000790656 pathogenic Niemann-Pick disease, type C2 2017-03-31 no assertion criteria provided clinical testing
Natera, Inc. RCV000008998 SCV001464118 pathogenic Niemann-Pick disease, type C2 2020-09-16 no assertion criteria provided clinical testing

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