NM_014946.4(SPAST):c.1238C>A (p.Ser413Ter) AND Hereditary spastic paraplegia 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 10, 2020
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:: RCV001383109.5

Allele description [Variation Report for NM_014946.4(SPAST):c.1238C>A (p.Ser413Ter)]

NM_014946.4(SPAST):c.1238C>A (p.Ser413Ter)

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.1238C>A (p.Ser413Ter)

HGVS:

NC_000002.12:g.32128472C>A
NG_008730.1:g.69862C>A
NM_001363823.2:c.1235C>A
NM_001363875.2:c.1139C>A
NM_001377959.1:c.1142C>A
NM_014946.3:c.1238C>A
NM_014946.4:c.1238C>AMANE SELECT
NM_199436.2:c.1142C>A
NP_001350752.1:p.Ser412Ter
NP_001350804.1:p.Ser380Ter
NP_001364888.1:p.Ser381Ter
NP_055761.2:p.Ser413Ter
NP_955468.1:p.Ser381Ter
LRG_714t1:c.1238C>A
LRG_714:g.69862C>A
NC_000002.11:g.32353541C>A

Protein change:

S380*

Links:

dbSNP: rs1553317045

NCBI 1000 Genomes Browser:

rs1553317045

Molecular consequence:

NM_001363823.2:c.1235C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001363875.2:c.1139C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001377959.1:c.1142C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_014946.4:c.1238C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_199436.2:c.1142C>A - 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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Homo sapiens tetraspanin 12 (TSPAN12), RefSeqGene on chromosome 7
Homo sapiens tetraspanin 12 (TSPAN12), RefSeqGene on chromosome 7
gi|299829216|ref|NG_023203.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001582134	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 10, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20932283, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582134

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 10, 2020)

germline

clinical testing

PubMed (2)
[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

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia.

Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz M, Alonso B, Corao AI, Gámez J, Esteban J, Gonzalo JF, Pascual-Pascual SI, López de Munain A, Moris G, Ribacoba R, Márquez C, Rosell J, Marín R, García-Barcina MJ, Del Castillo E, Benito C, Coto E; Group for the Study of the Genetics of Spastic Paraplegia..

BMC Neurol. 2010 Oct 8;10:89. doi: 10.1186/1471-2377-10-89.

PubMed [citation]

PMID:: 20932283
PMCID:: PMC2964648

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001582134.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ser413*) in the SPAST gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SPAST-related conditions. Loss-of-function variants in SPAST are known to be pathogenic (PMID: 20932283). 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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