Variant rs199874465 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000318.3(PEX2):c.769A>T(p.Ile257Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PEX2
NM_000318.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

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]

PEX2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23167899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX2	NM_000318.3 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	4/4	ENST00000357039.9	NP_000309.2	P28328
PEX2	NM_001079867.2 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	3/3		NP_001073336.2	P28328
PEX2	NM_001172086.2 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	5/5		NP_001165557.2	P28328
PEX2	NM_001172087.2 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	3/3		NP_001165558.2	P28328

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEX2	ENST00000357039.9 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	4/4	1	NM_000318.3	ENSP00000349543.4	P28328
PEX2	ENST00000522527.5 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	3/3	1		ENSP00000428638.1	P28328
PEX2	ENST00000520103.5 linkuse as main transcript	c.769A>T	p.Ile257Leu	missense_variant	3/3	2		ENSP00000428590.1	P28328

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251296

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135818

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461530

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

.;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.097

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.036

B;B;B

Vest4

0.36

MutPred

0.49

Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);

MVP

0.62

ClinPred

0.32

GERP RS

3.0

Varity_R

0.089

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over