Variant chr8-76983440-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5

The NM_000318.3(PEX2):c.739T>C(p.Cys247Arg) 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 Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C247Y) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

PEX2
NM_000318.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P: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]

PEX2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr8-76983439-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 265330.Status of the report is criteria_provided_single_submitter, 1 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.994

PP5

Variant 8-76983440-A-G is Pathogenic according to our data. Variant chr8-76983440-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 139589.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PEX2	NM_000318.3 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	4/4	ENST00000357039.9
PEX2	NM_001079867.2 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	3/3
PEX2	NM_001172086.2 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	5/5
PEX2	NM_001172087.2 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PEX2	ENST00000357039.9 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	4/4	1	NM_000318.3	P1
PEX2	ENST00000522527.5 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	3/3	1		P1
PEX2	ENST00000520103.5 linkuse as main transcript	c.739T>C	p.Cys247Arg	missense_variant	3/3	2		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Peroxisome biogenesis disorder 5A (Zellweger)

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.59

BayesDel_noAF

Pathogenic

0.61

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.92

D;D;D

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

.;.;T

M_CAP

Pathogenic

0.74

MetaRNN

Pathogenic

0.99

D;D;D

MetaSVM

Pathogenic

0.97

MutationAssessor

Pathogenic

3.4

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-12

D;D;D

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.95

MutPred

0.92

Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);

MVP

0.97

ClinPred

1.0

GERP RS

5.2

Varity_R

0.99

gMVP

0.92

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