ClinVar Genomic variation as it relates to human health
NM_001351132.2(PEX5):c.677dup (p.Val227fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001351132.2(PEX5):c.677dup (p.Val227fs)
Variation ID: 190410 Accession: VCV000190410.1
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 12p13.31 12: 7202274-7202275 (GRCh38) [ NCBI UCSC ] 12: 7354870-7354871 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 31, 2015 Dec 27, 2015 May 15, 2015 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001351132.2:c.677dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001338061.1:p.Val227fs frameshift NM_000319.5:c.677dup NP_000310.2:p.Val227fs frameshift NM_001131023.1:c.722dupA NM_001131023.2:c.722dup NP_001124495.1:p.Val242fs frameshift NM_001131024.2:c.643-337dup intron variant NM_001131025.2:c.677dup NP_001124497.1:p.Val227fs frameshift NM_001131026.2:c.677dup NP_001124498.1:p.Val227fs frameshift NM_001300789.3:c.677dup NP_001287718.2:p.Val227fs frameshift NM_001351124.3:c.643-337dup intron variant NM_001351126.2:c.643-337dup intron variant NM_001351127.2:c.643-337dup intron variant NM_001351128.2:c.643-337dup intron variant NM_001351130.3:c.643-337dup intron variant NM_001351131.2:c.677dup NP_001338060.1:p.Val227fs frameshift NM_001351133.2:c.677dup NP_001338062.1:p.Val227fs frameshift NM_001351134.2:c.677dup NP_001338063.1:p.Val227fs frameshift NM_001351135.3:c.688-337dup intron variant NM_001351136.2:c.677dup NP_001338065.1:p.Val227fs frameshift NM_001351137.3:c.643-337dup intron variant NM_001351138.2:c.688-337dup intron variant NM_001351139.2:c.643-337dup intron variant NM_001351140.2:c.643-337dup intron variant NM_001374645.1:c.643-337dup intron variant NM_001374646.1:c.643-337dup intron variant NM_001374647.2:c.677dup NP_001361576.1:p.Val227fs frameshift NM_001374648.2:c.643-337dup intron variant NM_001374649.2:c.643-337dup intron variant NC_000012.12:g.7202275dup NC_000012.11:g.7354871dup NG_008448.1:g.18113dup - Protein change
- V242fs, V227fs
- Other names
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- Canonical SPDI
- NC_000012.12:7202274:A:AA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| PEX5 | - | - |
GRCh38 GRCh38 GRCh37 |
991 | 1043 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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| Pathogenic (1) |
criteria provided, single submitter
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May 15, 2015 | RCV000186575.2 | |
| Pathogenic (1) |
no assertion criteria provided
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Jul 28, 2015 | RCV000202646.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(May 15, 2015)
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criteria provided, single submitter
Method: research
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Rhizomelic chondrodysplasia punctata (mild)
Affected status: yes
Allele origin:
germline
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Department of Medical Genetics, Oslo University Hospital
Accession: SCV000222895.1
First in ClinVar: Jul 31, 2015 Last updated: Jul 31, 2015
Comment:
While previous mutations in PEX5 caused Zellweger spectrum disorder, this variant was shown to affect only the PEX5L isoform and resulted in a defect in … (more)
While previous mutations in PEX5 caused Zellweger spectrum disorder, this variant was shown to affect only the PEX5L isoform and resulted in a defect in the peroxisomal import of PTS2-tagged proteins only, thus resulting in mild RCDP. (less)
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Observation 1:
Clinical Features:
growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including mild rhizomelic shortening of humeri (present) , … (more)
growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including mild rhizomelic shortening of humeri (present) , peripheral neuropathy (present) (less)
Sex: female
Tissue: skin
Method: Whole exome sequencing was used to identify the variant and Sanger sequencing to verify segregation. The biochemical profile in blood and fibroblasts indicated the patient had a selective defect in the peroxisomal import of PTS2-tagged proteins. Peroxisomal PTS2 import was restored following expression of PEX5L in cultured patient fibroblasts.
Observation 2:
Clinical Features:
congenital cataracts (present) , growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including chondrodysplasia punctata and … (more)
congenital cataracts (present) , growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including chondrodysplasia punctata and mild rhizomelic shortening of humeri (present) , peripheral neuropathy (present) , bronchial asthma (present) (less)
Sex: female
Tissue: skin
Method: Whole exome sequencing was used to identify the variant and Sanger sequencing to verify segregation. The biochemical profile in blood and fibroblasts indicated the patient had a selective defect in the peroxisomal import of PTS2-tagged proteins. Peroxisomal PTS2 import was restored following expression of PEX5L in cultured patient fibroblasts.
Observation 3:
Clinical Features:
congenital cataracts (present) , growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including chondrodysplasia punctata and … (more)
congenital cataracts (present) , growth delay (present) , microcephaly (present) , severe intellectual disability (present) , epilepsy (present) , skeletal abnormalities, including chondrodysplasia punctata and mild rhizomelic shortening of humeri (present) , peripheral neuropathy (present) , bronchial asthma (present) (less)
Sex: male
Tissue: skin
Method: Whole exome sequencing was used to identify the variant and Sanger sequencing to verify segregation. The biochemical profile in blood and fibroblasts indicated the patient had a selective defect in the peroxisomal import of PTS2-tagged proteins. Peroxisomal PTS2 import was restored following expression of PEX5L in cultured patient fibroblasts.
Observation 4:
Clinical Features:
congenital cataracts (present) , growth delay (present) , microcephaly (present) , severe intellectual disability (present)
Sex: female
Tissue: skin
Method: Whole exome sequencing was used to identify the variant. The biochemical profile in blood and fibroblasts indicated the patient had a selective defect in the peroxisomal import of PTS2-tagged proteins. Peroxisomal PTS2 import was restored following expression of PEX5L in cultured patient fibroblasts.
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Pathogenic
(Jul 28, 2015)
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no assertion criteria provided
Method: literature only
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RHIZOMELIC CHONDRODYSPLASIA PUNCTATA, TYPE 5
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000257599.1
First in ClinVar: Dec 27, 2015 Last updated: Dec 27, 2015 |
Comment on evidence:
In 3 sibs, born to consanguineous Pakistani parents, with rhizomelic chondrodysplasia punctata type 5 (RCDP5; 616716), Baroy et al. (2015) identified a homozygous 1-bp deletion … (more)
In 3 sibs, born to consanguineous Pakistani parents, with rhizomelic chondrodysplasia punctata type 5 (RCDP5; 616716), Baroy et al. (2015) identified a homozygous 1-bp deletion (c.722dupA, NM_001131023.1) in exon 9 (coding exon 7) of the long isoform of PEX5, resulting in a frameshift (Val242GlyfsTer33). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The same mutation was identified in an unrelated Pakistani girl, born to consanguineous Pakistani parents, with RCDP. Studies of peroxisomal parameters in cultured fibroblasts of this patient had indicated a PTS2 protein import defect; no mutation was identified in PEX7 (601757). Baroy et al. (2015) showed that, similar to mutations in PEX7, loss of the PEX5-long isoform results in peroxisomal dysfunction due to selective defect in the import of PTS2-tagged proteins, causing RCDP instead of a peroxisome biogenesis disorder. Baroy et al. (2015) demonstrated that expression of the PEX5-long isoform restored the import of PTS2-tagged proteins in patient fibroblasts. (less)
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Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform. | Barøy T | Human molecular genetics | 2015 | PMID: 26220973 |
Text-mined citations for rs796051881 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.