ClinVar Genomic variation as it relates to human health
NM_025137.4(SPG11):c.529_533del (p.Ile177fs)
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_025137.4(SPG11):c.529_533del (p.Ile177fs)
Variation ID: 1110 Accession: VCV000001110.10
- Type and length
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Microsatellite, 5 bp
- Location
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Cytogenetic: 15q21.1 15: 44659213-44659217 (GRCh38) [ NCBI UCSC ] 15: 44951411-44951415 (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 May 3, 2013 Feb 14, 2024 Aug 27, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_025137.4:c.529_533del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_079413.3:p.Ile177fs frameshift NM_001160227.2:c.529_533del NP_001153699.1:p.Ile177fs frameshift NC_000015.10:g.44659213AATAT[1] NC_000015.9:g.44951411AATAT[1] NG_008885.1:g.9457ATATT[1] - Protein change
- I177fs
- Other names
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- Canonical SPDI
- NC_000015.10:44659212:AATATAATAT:AATAT
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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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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SPG11 | - | - |
GRCh38 GRCh37 |
3218 | 3318 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (6) |
criteria provided, multiple submitters, no conflicts
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Aug 27, 2022 | RCV000001169.15 | |
Pathogenic (1) |
no assertion criteria provided
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Nov 10, 2015 | RCV000202378.2 |
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
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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
Help
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 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001139575.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Pathogenic
(Jan 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002061250.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
Comment:
The c.529_533del;p.(Ile177Serfs*2) is a null frameshift variant (NMD) in the SPG11 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a … (more)
The c.529_533del;p.(Ile177Serfs*2) is a null frameshift variant (NMD) in the SPG11 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevantexon to the transcript -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 1110; OMIM: 610844.0002; PMID: 26556829; 19105190; 17322883) - PS4. The variant is present at low allele frequencies population databases (rs312262716– gnomAD 0.0006568%; ABraOM 0.000427 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Ile177Serfs*2) was detected in trans with a pathogenic variant (PMID: 26556829; 19105190) - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 26556829; 19105190) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: unknown
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002762892.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Aug 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002194060.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1110). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1110). This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 17322883). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile177Serfs*2) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). (less)
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Pathogenic
(Nov 10, 2015)
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no assertion criteria provided
Method: literature only
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SPASTIC PARAPLEGIA 11, AUTOSOMAL RECESSIVE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000021319.3
First in ClinVar: Apr 04, 2013 Last updated: Jan 10, 2016 |
Comment on evidence:
In 2 Portuguese families, Stevanin et al. (2007) found that a 5-bp deletion in exon 3 of the SPG11 gene, 529_533delATATT, in homozygosity segregated with … (more)
In 2 Portuguese families, Stevanin et al. (2007) found that a 5-bp deletion in exon 3 of the SPG11 gene, 529_533delATATT, in homozygosity segregated with spastic paraplegia with thin corpus callosum (SPG11; 604360). The mutation was predicted to lead to a frameshift with early termination at amino acid residue 179 (I177_I178delfsX). In 3 Italian sibs (family RM-801) with axonal Charcot-Marie-Tooth disease type 2X (CMT2X; 616668), Montecchiani et al. (2016) identified compound heterozygous mutations in the SPG11 gene: c.529_533delATATT, predicted to result in a frameshift and premature termination (Ile177SerfsTer2), and a c.592C-T transition in exon 3 of the SPG11 gene, resulting in a gln198-to-ter substitution (Q198X; 610844.0015). The patients also had thin corpus callosum and mild cognitive impairment. The mutation, which was found by linkage analysis and candidate gene sequencing, segregated with the disorder in the family and was not found in 300 control chromosomes. Functional studies of the variants were not performed. (less)
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Pathogenic
(Nov 10, 2015)
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no assertion criteria provided
Method: literature only
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CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2X
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000257389.2
First in ClinVar: Dec 05, 2015 Last updated: Jan 10, 2016 |
Comment on evidence:
In 2 Portuguese families, Stevanin et al. (2007) found that a 5-bp deletion in exon 3 of the SPG11 gene, 529_533delATATT, in homozygosity segregated with … (more)
In 2 Portuguese families, Stevanin et al. (2007) found that a 5-bp deletion in exon 3 of the SPG11 gene, 529_533delATATT, in homozygosity segregated with spastic paraplegia with thin corpus callosum (SPG11; 604360). The mutation was predicted to lead to a frameshift with early termination at amino acid residue 179 (I177_I178delfsX). In 3 Italian sibs (family RM-801) with axonal Charcot-Marie-Tooth disease type 2X (CMT2X; 616668), Montecchiani et al. (2016) identified compound heterozygous mutations in the SPG11 gene: c.529_533delATATT, predicted to result in a frameshift and premature termination (Ile177SerfsTer2), and a c.592C-T transition in exon 3 of the SPG11 gene, resulting in a gln198-to-ter substitution (Q198X; 610844.0015). The patients also had thin corpus callosum and mild cognitive impairment. The mutation, which was found by linkage analysis and candidate gene sequencing, segregated with the disorder in the family and was not found in 300 control chromosomes. Functional studies of the variants were not performed. (less)
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not provided
(-)
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no classification provided
Method: literature only
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Hereditary spastic paraplegia 11
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000058160.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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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
HelpTitle | Author | Journal | Year | Link |
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Spastic Paraplegia 11. | Adam MP | - | 2019 | PMID: 20301389 |
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. | Montecchiani C | Brain : a journal of neurology | 2016 | PMID: 26556829 |
Exome sequencing reveals SPG11 mutations causing juvenile ALS. | Daoud H | Neurobiology of aging | 2012 | PMID: 22154821 |
SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis. | Orlacchio A | Brain : a journal of neurology | 2010 | PMID: 20110243 |
Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion. | Denora PS | Human mutation | 2009 | PMID: 19105190 |
Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. | Stevanin G | Nature genetics | 2007 | PMID: 17322883 |
Text-mined citations for rs312262716 ...
HelpRecord last updated Feb 14, 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.