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NM_014946.4(SPAST):c.237C>A (p.Cys79Ter) AND Hereditary spastic paraplegia 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 15, 2023
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:
RCV002871697.2

Allele description

NM_014946.4(SPAST):c.237C>A (p.Cys79Ter)

Gene:
SPAST:spastin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p22.3
Genomic location:
Preferred name:
NM_014946.4(SPAST):c.237C>A (p.Cys79Ter)
HGVS:
  • NC_000002.12:g.32064068C>A
  • NG_008730.1:g.5458C>A
  • NG_094904.1:g.701C>A
  • NM_001363823.2:c.237C>A
  • NM_001363875.2:c.237C>A
  • NM_001377959.1:c.237C>A
  • NM_014946.4:c.237C>AMANE SELECT
  • NM_199436.2:c.237C>A
  • NP_001350752.1:p.Cys79Ter
  • NP_001350804.1:p.Cys79Ter
  • NP_001364888.1:p.Cys79Ter
  • NP_055761.2:p.Cys79Ter
  • NP_055761.2:p.Cys79Ter
  • NP_955468.1:p.Cys79Ter
  • LRG_714t1:c.237C>A
  • LRG_714:g.5458C>A
  • LRG_714p1:p.Cys79Ter
  • NC_000002.11:g.32289137C>A
  • NM_014946.3:c.237C>A
Protein change:
C79*
Molecular consequence:
  • NM_001363823.2:c.237C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001363875.2:c.237C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001377959.1:c.237C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014946.4:c.237C>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_199436.2:c.237C>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003234278Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 15, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 Invitae, SCV003234278.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2027106). This variant has not been reported in the literature in individuals affected with SPAST-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys79*) 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).

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

Last Updated: Feb 28, 2024