NM_014946.4(SPAST):c.1245del (p.Lys414_Tyr415insTer) AND Hereditary spastic paraplegia 4

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2017
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:: RCV000200188.7

Allele description

NM_014946.4(SPAST):c.1245del (p.Lys414_Tyr415insTer)

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.1245del (p.Lys414_Tyr415insTer)

HGVS:

NC_000002.12:g.32128479del
NG_008730.1:g.69869del
NM_001363823.2:c.1242del
NM_001363875.2:c.1146del
NM_001377959.1:c.1149del
NM_014946.4:c.1245delMANE SELECT
NM_199436.2:c.1149del
NP_001350752.1:p.Lys413_Tyr414insTer
NP_001350804.1:p.Lys381_Tyr382insTer
NP_001364888.1:p.Lys382_Tyr383insTer
NP_055761.2:p.Lys414_Tyr415insTer
NP_955468.1:p.Lys382_Tyr383insTer
LRG_714t1:c.1245del
LRG_714:g.69869del
NC_000002.11:g.32353548del
NM_014946.3:c.1245del
NM_014946.3:c.1245delC

Links:

dbSNP: rs863224513

NCBI 1000 Genomes Browser:

rs863224513

Molecular consequence:

NM_001363823.2:c.1242del - nonsense - [Sequence Ontology: SO:0001587]
NM_001363875.2:c.1146del - nonsense - [Sequence Ontology: SO:0001587]
NM_001377959.1:c.1149del - nonsense - [Sequence Ontology: SO:0001587]
NM_014946.4:c.1245del - nonsense - [Sequence Ontology: SO:0001587]
NM_199436.2:c.1149del - nonsense - [Sequence Ontology: SO:0001587]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000253913	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18701882, 19875132, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000253913

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2017)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia.

Shoukier M, Neesen J, Sauter SM, Argyriou L, Doerwald N, Pantakani DV, Mannan AU.

Eur J Hum Genet. 2009 Feb;17(2):187-94. doi: 10.1038/ejhg.2008.147. Epub 2008 Aug 13. Erratum in: Eur J Hum Genet. 2009 Mar;17(3):401-2.

PubMed [citation]

PMID:: 18701882
PMCID:: PMC2986068

Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia.

Magariello A, Muglia M, Patitucci A, Ungaro C, Mazzei R, Gabriele AL, Sprovieri T, Citrigno L, Conforti FL, Liguori M, Gambardella A, Bono F, Piccoli T, Patti F, Zappia M, Mancuso M, Iemolo F, Quattrone A.

J Neurol Sci. 2010 Jan 15;288(1-2):96-100. doi: 10.1016/j.jns.2009.09.025. Epub 2009 Oct 28.

PubMed [citation]

PMID:: 19875132

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000253913.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Truncating variants in SPAST are known to be pathogenic. This variation has been reported in individuals affected with hereditary spastic paraplegia (PMID: 18701882, 19875132). This sequence change deletes 1 nucleotide in exon 9 of the SPAST mRNA (c.1245delC), causing a frameshift at codon 415. This creates a premature translational stop signal (p.Tyr415*) and is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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