ClinVar Miner

Submissions for variant NM_006432.4(NPC2):c.190+5G>A (rs80358268)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000009000 SCV000784506 uncertain significance Niemann-Pick disease, type C2 2018-03-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV000009000 SCV000807237 pathogenic Niemann-Pick disease, type C2 2017-09-01 criteria provided, single submitter clinical testing This variant has been previously reported as disease-causing and was found once in our laboratory homozygous in a 14-year-old male with intellectual disability, epilepsy, similarly affected sibling
Invitae RCV000009000 SCV000953622 likely pathogenic Niemann-Pick disease, type C2 2018-10-29 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the NPC2 gene. It does not directly change the encoded amino acid sequence of the NPC2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs80358268, ExAC 0.1%). This variant has been observed in individuals affected with Niemann-Pick type C disease (PMID: 11567215, 28105569). It is also known as IVS2+5G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 8479). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 11567215). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000009000 SCV000029214 pathogenic Niemann-Pick disease, type C2 2001-11-01 no assertion criteria provided literature only
GeneReviews RCV000009000 SCV000041168 pathologic Niemann-Pick disease, type C2 2008-07-22 no assertion criteria provided curation Converted during submission to Pathogenic.

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