Variant 8-76983806-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000318.3(PEX2):c.373C>A(p.Arg125=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,461,828 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R125R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PEX2
NM_000318.3 synonymous

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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]

PEX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PEX2	NM_000318.3 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	4/4	ENST00000357039.9
PEX2	NM_001079867.2 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	3/3
PEX2	NM_001172086.2 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	5/5
PEX2	NM_001172087.2 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PEX2	ENST00000357039.9 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	4/4	1	NM_000318.3	P1
PEX2	ENST00000522527.5 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	3/3	1		P1
PEX2	ENST00000520103.5 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	3/3	2		P1
PEX2	ENST00000518986.5 linkuse as main transcript	c.373C>A	p.Arg125=	synonymous_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251382

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 5A (Zellweger)

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 10, 2021

This variant has not been reported in the literature in individuals affected with PEX2-related conditions. This variant is present in population databases (rs61752124, ExAC 0.006%). This sequence change affects codon 125 of the PEX2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PEX2 protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

DANN

Benign

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over