rs587776893
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_007175.8(ERLIN2):c.812_813insAC(p.Asn272ProfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
ERLIN2
NM_007175.8 frameshift
NM_007175.8 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.73
Genes affected
ERLIN2 (HGNC:1356): (ER lipid raft associated 2) This gene encodes a member of the SPFH domain-containing family of lipid raft-associated proteins. The encoded protein is localized to lipid rafts of the endoplasmic reticulum and plays a critical role in inositol 1,4,5-trisphosphate (IP3) signaling by mediating ER-associated degradation of activated IP3 receptors. Mutations in this gene are a cause of spastic paraplegia-18 (SPG18). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.205 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 8-37753521-G-GCA is Pathogenic according to our data. Variant chr8-37753521-G-GCA is described in ClinVar as [Pathogenic]. Clinvar id is 30913.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ERLIN2 | NM_007175.8 | c.812_813insAC | p.Asn272ProfsTer4 | frameshift_variant | 11/12 | ENST00000519638.3 | NP_009106.1 | |
ERLIN2 | NM_001362878.2 | c.812_813insAC | p.Asn272ProfsTer4 | frameshift_variant | 11/12 | NP_001349807.1 | ||
ERLIN2 | XM_047421307.1 | c.812_813insAC | p.Asn272ProfsTer4 | frameshift_variant | 12/13 | XP_047277263.1 | ||
ERLIN2 | XM_047421308.1 | c.566_567insAC | p.Asn190ProfsTer4 | frameshift_variant | 8/9 | XP_047277264.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERLIN2 | ENST00000519638.3 | c.812_813insAC | p.Asn272ProfsTer4 | frameshift_variant | 11/12 | 2 | NM_007175.8 | ENSP00000428112 | P1 | |
ERLIN2 | ENST00000521644.5 | c.812_813insAC | p.Asn272ProfsTer4 | frameshift_variant | 11/12 | 5 | ENSP00000429621 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 18 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at