NM_000466.3(PEX1):c.2071+1G>T AND Zellweger spectrum disorders

Clinical significance:Likely pathogenic (Last evaluated: Mar 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001377623.1

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:
Zellweger spectrum disorders (ZS)
Synonyms:
Zellweger syndrome; Zellweger Spectrum Disorder; Zellweger Spectrum
Identifiers:
MONDO: MONDO:0019609; MedGen: C0043459; Orphanet: 912

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001575005Invitaecriteria provided, single submitter
Likely pathogenic
(Mar 17, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels.

Walter C, Gootjes J, Mooijer PA, Portsteffen H, Klein C, Waterham HR, Barth PG, Epplen JT, Kunau WH, Wanders RJ, Dodt G.

Am J Hum Genet. 2001 Jul;69(1):35-48. Epub 2001 Jun 1.

PubMed [citation]
PMID:
11389485
PMCID:
PMC1226046

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001575005.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change affects a donor splice site in intron 12 of the PEX1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with infantile Refsum disease (PMID: 11389485). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Jan 8, 2022

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