NM_014946.4(SPAST):c.340G>T (p.Glu114Ter) AND Hereditary spastic paraplegia 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 28, 2022
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:: RCV001960327.6

Allele description [Variation Report for NM_014946.4(SPAST):c.340G>T (p.Glu114Ter)]

NM_014946.4(SPAST):c.340G>T (p.Glu114Ter)

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.340G>T (p.Glu114Ter)

HGVS:

NC_000002.12:g.32064171G>T
NG_008730.1:g.5561G>T
NM_001363823.2:c.340G>T
NM_001363875.2:c.340G>T
NM_001377959.1:c.340G>T
NM_014946.3:c.340G>T
NM_014946.4:c.340G>TMANE SELECT
NM_199436.2:c.340G>T
NP_001350752.1:p.Glu114Ter
NP_001350804.1:p.Glu114Ter
NP_001364888.1:p.Glu114Ter
NP_055761.2:p.Glu114Ter
NP_955468.1:p.Glu114Ter
LRG_714t1:c.340G>T
LRG_714:g.5561G>T
NC_000002.11:g.32289240G>T

Protein change:

E114*

Links:

dbSNP: rs1553394608

NCBI 1000 Genomes Browser:

rs1553394608

Molecular consequence:

NM_001363823.2:c.340G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363875.2:c.340G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001377959.1:c.340G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014946.4:c.340G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_199436.2:c.340G>T - 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
SCV002226468	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 28, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11309678, 31227335, 20932283, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002226468

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 28, 2022)

germline

clinical testing

PubMed (4)
[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

Identification and expression analysis of spastin gene mutations in hereditary spastic paraplegia.

Svenson IK, Ashley-Koch AE, Gaskell PC, Riney TJ, Cumming WJ, Kingston HM, Hogan EL, Boustany RM, Vance JM, Nance MA, Pericak-Vance MA, Marchuk DA.

Am J Hum Genet. 2001 May;68(5):1077-85. Epub 2001 Apr 16.

PubMed [citation]

PMID:: 11309678
PMCID:: PMC1226088

Chinese patients with adrenoleukodystrophy and Zellweger spectrum disorder presenting with hereditary spastic paraplegia.

Chen YJ, Wang MW, Dong EL, Lin XH, Wang N, Zhang ZQ, Lin X, Chen WJ.

Parkinsonism Relat Disord. 2019 Aug;65:256-260. doi: 10.1016/j.parkreldis.2019.06.008. Epub 2019 Jun 9.

PubMed [citation]

PMID:: 31227335

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002226468.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is also known as c.465G>T. This premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 11309678, 31227335). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu114*) in the SPAST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). ClinVar contains an entry for this variant (Variation ID: 1442664). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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