Variant 8-76980598-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000318.3(PEX2):c.*2663T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,020 control chromosomes in the GnomAD database, including 21,288 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 21286 hom., cov: 32)

Exomes 𝑓: 0.44 ( 2 hom. )

Consequence

PEX2
NM_000318.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.320

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 8-76980598-A-T is Benign according to our data. Variant chr8-76980598-A-T is described in ClinVar as [Benign]. Clinvar id is 363772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PEX2	NM_000318.3 linkuse as main transcript	c.*2663T>A	3_prime_UTR_variant	4/4	ENST00000357039.9
PEX2	NM_001079867.2 linkuse as main transcript	c.*2663T>A	3_prime_UTR_variant	3/3
PEX2	NM_001172086.2 linkuse as main transcript	c.*2663T>A	3_prime_UTR_variant	5/5
PEX2	NM_001172087.2 linkuse as main transcript	c.*2663T>A	3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX2	ENST00000357039.9 linkuse as main transcript	c.*2663T>A		3_prime_UTR_variant	4/4	1	NM_000318.3	P1

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77910

AN:

151886

Hom.:

21277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.520

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.551

GnomAD4 exome

AF:

0.438

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.429

GnomAD4 genome

AF:

0.513

AC:

77938

AN:

152004

Hom.:

21286

Cov.:

AF XY:

0.512

AC XY:

38041

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.625

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.477

Gnomad4 NFE

AF:

0.591

Gnomad4 OTH

AF:

0.553

Alfa

AF:

0.520

Hom.:

2329

Bravo

AF:

0.513

Asia WGS

AF:

0.518

AC:

1804

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Peroxisome biogenesis disorder 5A (Zellweger)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.86

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