rs80358267
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_006432.5(NPC2):c.27del(p.Leu10SerfsTer25) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L9L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
NPC2
NM_006432.5 frameshift
NM_006432.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.612
Genes affected
NPC2 (HGNC:14537): (NPC intracellular cholesterol transporter 2) This gene encodes a protein containing a lipid recognition domain. The encoded protein may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 46 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-74493247-GC-G is Pathogenic according to our data. Variant chr14-74493247-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 21457.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-74493247-GC-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPC2 | NM_006432.5 | c.27del | p.Leu10SerfsTer25 | frameshift_variant | 1/5 | ENST00000555619.6 | |
NPC2 | NM_001363688.1 | c.27del | p.Leu10SerfsTer25 | frameshift_variant | 1/4 | ||
NPC2 | NM_001375440.1 | c.27del | p.Leu10SerfsTer25 | frameshift_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPC2 | ENST00000555619.6 | c.27del | p.Leu10SerfsTer25 | frameshift_variant | 1/5 | 1 | NM_006432.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Niemann-Pick disease, type C2 Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2001 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at