chr8-76983431-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000318.3(PEX2):​c.748T>G​(p.Trp250Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W250R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PEX2
NM_000318.3 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.73
Variant links:
Genes affected
PEX2 (HGNC:9717): (peroxisomal biogenesis factor 2) This gene encodes an integral peroxisomal membrane protein required for peroxisome biogenesis. The protein is thought to be involved in peroxisomal matrix protein import. Mutations in this gene result in one form of Zellweger syndrome and infantile Refsum disease. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEX2NM_000318.3 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 4/4 ENST00000357039.9 NP_000309.2
PEX2NM_001079867.2 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 3/3 NP_001073336.2
PEX2NM_001172086.2 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 5/5 NP_001165557.2
PEX2NM_001172087.2 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 3/3 NP_001165558.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEX2ENST00000357039.9 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 4/41 NM_000318.3 ENSP00000349543 P1
PEX2ENST00000522527.5 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 3/31 ENSP00000428638 P1
PEX2ENST00000520103.5 linkuse as main transcriptc.748T>G p.Trp250Gly missense_variant 3/32 ENSP00000428590 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 02, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.070
CADD
Pathogenic
28
DANN
Benign
0.96
DEOGEN2
Uncertain
0.69
D;D;D
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
.;.;T
M_CAP
Uncertain
0.19
D
MetaRNN
Pathogenic
0.89
D;D;D
MetaSVM
Uncertain
0.33
D
MutationAssessor
Uncertain
2.6
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Pathogenic
0.72
Sift
Benign
0.47
T;T;T
Sift4G
Benign
0.62
T;T;T
Polyphen
0.98
D;D;D
Vest4
0.83
MutPred
0.70
Loss of catalytic residue at M253 (P = 0.0094);Loss of catalytic residue at M253 (P = 0.0094);Loss of catalytic residue at M253 (P = 0.0094);
MVP
0.95
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.47
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142645936; hg19: chr8-77895667; API