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NM_025137.3(SPG11):c.5456_5457del (p.Glu1819Alafs) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 3, 2021
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:
RCV002345267.2

Allele description [Variation Report for NM_025137.3(SPG11):c.5456_5457del (p.Glu1819Alafs)]

NM_025137.3(SPG11):c.5456_5457del (p.Glu1819Alafs)

Gene:
SPG11:SPG11 vesicle trafficking associated, spatacsin [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_025137.3(SPG11):c.5456_5457del (p.Glu1819Alafs)
HGVS:
  • NC_000015.10:g.44584223CT[1]
  • NG_008885.1:g.84453AG[1]
  • NM_001160227.2:c.5456_5457del
  • NM_025137.4:c.5456_5457delMANE SELECT
  • NP_001153699.1:p.Glu1819fs
  • NP_079413.3:p.Glu1819fs
  • NC_000015.9:g.44876421CT[1]
  • NC_000015.9:g.44876421_44876422del
  • NM_025137.3:c.5456_5457del
  • NM_025137.3:c.5456_5457delAG
  • NM_025137.3:c.insA
Protein change:
E1819fs
Links:
dbSNP: rs312262764
NCBI 1000 Genomes Browser:
rs312262764
Molecular consequence:
  • NM_001160227.2:c.5456_5457del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_025137.4:c.5456_5457del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002649117Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Feb 3, 2021) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia.

Paisan-Ruiz C, Dogu O, Yilmaz A, Houlden H, Singleton A.

Neurology. 2008 Apr 15;70(16 Pt 2):1384-9. doi: 10.1212/01.wnl.0000294327.66106.3d. Epub 2008 Mar 12.

PubMed [citation]
PMID:
18337587
PMCID:
PMC2730021

Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia.

Fogel BL, Lee H, Deignan JL, Strom SP, Kantarci S, Wang X, Quintero-Rivera F, Vilain E, Grody WW, Perlman S, Geschwind DH, Nelson SF.

JAMA Neurol. 2014 Oct;71(10):1237-46. doi: 10.1001/jamaneurol.2014.1944. Erratum in: JAMA Neurol. 2015 Jan;72(1):128.

PubMed [citation]
PMID:
25133958
PMCID:
PMC4324730
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002649117.2

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

Description

The c.5456_5457delAG pathogenic mutation, located in coding exon 30 of the SPG11 gene, results from a deletion of two nucleotides at nucleotide positions 5456 to 5457, causing a translational frameshift with a predicted alternate stop codon (p.E1819Afs*10). This mutation was detected in a compound heterozygous state with other truncating alterations in SPG11 in two siblings and one additional unrelated individual, all of whom had phenotypes consistent with hereditary spastic paraplegia (Paisan-Ruiz C et al. Neurology, 2008 Apr;70:1384-9; Kara E et al. Brain, 2016 07;139:1904-18). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024