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NM_000287.4(PEX6):c.1947del (p.Ile650fs) AND Peroxisome biogenesis disorder 4B

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jul 17, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000665650.2

Allele description [Variation Report for NM_000287.4(PEX6):c.1947del (p.Ile650fs)]

NM_000287.4(PEX6):c.1947del (p.Ile650fs)

Gene:
PEX6:peroxisomal biogenesis factor 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
6p21.1
Genomic location:
Preferred name:
NM_000287.4(PEX6):c.1947del (p.Ile650fs)
HGVS:
  • NC_000006.12:g.42966797del
  • NG_008370.1:g.17448del
  • NM_000287.4:c.1947delMANE SELECT
  • NM_001316313.2:c.1683del
  • NP_000278.3:p.Ile650fs
  • NP_001303242.1:p.Ile562fs
  • NC_000006.11:g.42934534del
  • NC_000006.11:g.42934535del
  • NM_000287.3:c.1947del
  • NM_000287.3:c.1947delG
  • NR_133009.2:n.1978del
Protein change:
I562fs
Links:
dbSNP: rs267608227
NCBI 1000 Genomes Browser:
rs267608227
Molecular consequence:
  • NM_000287.4:c.1947del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001316313.2:c.1683del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_133009.2:n.1978del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Peroxisome biogenesis disorder 4B (PBD4B)
Identifiers:
MONDO: MONDO:0013931; MedGen: C3553937; Orphanet: 44; OMIM: 614863

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000789804Counsyl
no assertion criteria provided
Pathogenic
(Feb 21, 2017) 		unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV005400229Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jul 17, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Rational diagnostic strategy for Zellweger syndrome spectrum patients.

Krause C, Rosewich H, Gärtner J.

Eur J Hum Genet. 2009 Jun;17(6):741-8. doi: 10.1038/ejhg.2008.252. Epub 2009 Jan 14.

PubMed [citation]
PMID:
19142205
PMCID:
PMC2947092

Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients.

Ebberink MS, Kofster J, Wanders RJ, Waterham HR.

Hum Mutat. 2010 Jan;31(1):E1058-70. doi: 10.1002/humu.21153.

PubMed [citation]
PMID:
19877282
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000789804.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV005400229.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with peroxisome biogenesis disorder 4B (MIM#614863), Heimler syndrome 2 (MIM#616617) and peroxisome biogenesis disorder 4A (Zellweger; MIM#614862). (I) 0108 - This gene is associated with both recessive and dominant disease. The recurrent variant p.(Arg860Trp) is associated with autosomal dominant peroxisome biogenesis disorder 4B (PMID: 29220678). In addition, Heimler syndrome 2 is milder due to one allele encoding for a protein with residual function (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 (6 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic, and observed in both homozygous and heterozygous individuals with Zellweger syndrome (PMID: 19877282). (SP) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Dec 22, 2024