U.S. flag

An official website of the United States government

NM_014946.4(SPAST):c.1246-2896_1493+523dup AND Hereditary spastic paraplegia 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 2007
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000006031.5

Allele description [Variation Report for NM_014946.4(SPAST):c.1246-2896_1493+523dup]

NM_014946.4(SPAST):c.1246-2896_1493+523dup

Gene:
SPAST:spastin [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p22.3
Genomic location:
Preferred name:
NM_014946.4(SPAST):c.1246-2896_1493+523dup
Other names:
SPAST, EX10-12DUP
HGVS:
  • NC_000002.12:g.32133667_32137711dup
  • NG_008730.1:g.75057_79101dup
  • NM_001363823.2:c.1243-2896_1490+523dup
  • NM_001363875.2:c.1147-2896_1394+523dup
  • NM_001377959.1:c.1150-2896_1397+523dup
  • NM_014946.4:c.1246-2896_1493+523dupMANE SELECT
  • NM_199436.2:c.1150-2896_1397+523dup
  • LRG_714:g.75057_79101dup
  • NC_000002.11:g.32358736_32362780dup
Note:
NCBI staff reviewed the sequence information reported in PubMed 17895902 supplementary figure to determine the location of this allele on the current reference sequence.
Links:
dbVar: nssv7487215; dbVar: nsv1197506; OMIM: 604277.0022
Molecular consequence:
  • NM_001363823.2:c.1243-2896_1490+523dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363875.2:c.1147-2896_1394+523dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001377959.1:c.1150-2896_1397+523dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_014946.4:c.1246-2896_1493+523dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_199436.2:c.1150-2896_1397+523dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001363823.2:c.1243-2896_1490+523dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363875.2:c.1147-2896_1394+523dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001377959.1:c.1150-2896_1397+523dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_014946.4:c.1246-2896_1493+523dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_199436.2:c.1150-2896_1397+523dup - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Hereditary spastic paraplegia 4
Synonyms:
Spastic paraplegia 4, autosomal dominant; Familial spastic paraplegia autosomal dominant 2
Identifiers:
MONDO: MONDO:0008438; MedGen: C1866855; Orphanet: 100985; OMIM: 182601

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000026213OMIM
no assertion criteria provided
Pathogenic
(Dec 1, 2007) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Autosomal dominant (AD) pure spastic paraplegia (HSP) linked to locus SPG4 affects almost exclusively males in a large pedigree.

Starling A, Rocco P, Passos-Bueno MR, Hazan J, Marie SK, Zatz M.

J Med Genet. 2002 Dec;39(12):e77. No abstract available.

PubMed [citation]
PMID:
12471215
PMCID:
PMC1757223

A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree.

Mitne-Neto M, Kok F, Beetz C, Pessoa A, Bueno C, Graciani Z, Martyn M, Monteiro CB, Mitne G, Hubert P, Nygren AO, Valadares M, Cerqueira AM, Starling A, Deufel T, Zatz M.

Eur J Hum Genet. 2007 Dec;15(12):1276-9. Epub 2007 Sep 26.

PubMed [citation]
PMID:
17895902

Details of each submission

From OMIM, SCV000026213.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In affected individuals of a large Brazilian kindred with spastic paraplegia-4 (SPG4; 182601), originally reported by Starling et al. (2002), Mitne-Neto et al. (2007) identified a heterozygous tandem duplication of exons 10 through 12 of the SPAST gene. Long-range PCR and sequencing showed nonhomology of the sequences contributing to the novel fusion. The duplication was predicted to result in premature termination and disruption of enzymatic activity. Twelve of 30 mutation carriers had no clinical complaints. Among these patients, 9 of 14 female carriers had no complaints, indicating sex-dependent penetrance in this family, with women being partially protected.

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

Last Updated: Apr 23, 2022