rs149254654
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_007175.8(ERLIN2):c.589G>A(p.Ala197Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
ERLIN2
NM_007175.8 missense
NM_007175.8 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 7.76
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_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ERLIN2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.34910873).
BP6
?
Variant 8-37750426-G-A is Benign according to our data. Variant chr8-37750426-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435089.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERLIN2 | NM_007175.8 | c.589G>A | p.Ala197Thr | missense_variant | 9/12 | ENST00000519638.3 | |
ERLIN2 | NM_001362878.2 | c.589G>A | p.Ala197Thr | missense_variant | 9/12 | ||
ERLIN2 | XM_047421307.1 | c.589G>A | p.Ala197Thr | missense_variant | 10/13 | ||
ERLIN2 | XM_047421308.1 | c.343G>A | p.Ala115Thr | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERLIN2 | ENST00000519638.3 | c.589G>A | p.Ala197Thr | missense_variant | 9/12 | 2 | NM_007175.8 | P1 | |
ERLIN2 | ENST00000521644.5 | c.589G>A | p.Ala197Thr | missense_variant | 9/12 | 5 | |||
ERLIN2 | ENST00000518526.5 | c.460G>A | p.Ala154Thr | missense_variant | 7/8 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250998Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135664
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461448Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727008
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74314
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 03, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2023 | The c.589G>A (p.A197T) alteration is located in exon 9 (coding exon 8) of the ERLIN2 gene. This alteration results from a G to A substitution at nucleotide position 589, causing the alanine (A) at amino acid position 197 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.90
.;P;P;.
Vest4
0.31
MVP
MPC
1.6
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at