NM_000466.3(PEX1):c.2071+1G>T AND Peroxisome biogenesis disorder

Clinical significance:Pathogenic (Last evaluated: May 31, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001193609.1

Allele description [Variation Report for NM_000466.3(PEX1):c.2071+1G>T]

NM_000466.3(PEX1):c.2071+1G>T

Gene:
PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.2
Genomic location:
Preferred name:
NM_000466.3(PEX1):c.2071+1G>T
HGVS:
  • NC_000007.14:g.92504731C>A
  • NG_008341.1:g.28801G>T
  • NG_008341.2:g.28801G>T
  • NM_000466.3:c.2071+1G>TMANE SELECT
  • NM_001282677.2:c.1900+1517G>T
  • NM_001282678.2:c.1447+1G>T
  • NC_000007.13:g.92134045C>A
  • NM_000466.2:c.2071+1G>T
Links:
dbSNP: rs267608177
NCBI 1000 Genomes Browser:
rs267608177
Molecular consequence:
  • NM_001282677.2:c.1900+1517G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000466.3:c.2071+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001282678.2:c.1447+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Peroxisome biogenesis disorder (PBD, ZSS)
Synonyms:
PEROXISOME BIOGENESIS DISORDER (NEONATAL ADRENOLEUKODYSTROPHY/INFANTILE REFSUM DISEASE); INFANTILE PHYTANIC ACID STORAGE DISEASE; PEROXISOME BIOGENESIS DISORDER (NALD/IRD); See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0019234; MedGen: C1832200; OMIM: PS214100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001362557Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(May 31, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.

Ebberink MS, Mooijer PA, Gootjes J, Koster J, Wanders RJ, Waterham HR.

Hum Mutat. 2011 Jan;32(1):59-69. doi: 10.1002/humu.21388.

PubMed [citation]
PMID:
21031596

Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood.

Berendse K, Engelen M, Ferdinandusse S, Majoie CB, Waterham HR, Vaz FM, Koelman JH, Barth PG, Wanders RJ, Poll-The BT.

J Inherit Metab Dis. 2016 Jan;39(1):93-106. doi: 10.1007/s10545-015-9880-2. Epub 2015 Aug 19.

PubMed [citation]
PMID:
26287655
PMCID:
PMC4710674
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362557.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: PEX1 c.2071+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: 4/5 predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250890 control chromosomes. c.2071+1G>T has been reported in the literature in multiple individuals affected with Zellweger Syndrome (Walter_2001, Ebberink_2010, Berendse_2015). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence demonstrating a reduction in PEX1 protein expression in fibroblasts cultured from an individual with this variant (Walter_2001). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 8, 2022

Support Center