NM_014946.4(SPAST):c.1245+1G>C AND Hereditary spastic paraplegia 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 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:: RCV002664229.3

Allele description [Variation Report for NM_014946.4(SPAST):c.1245+1G>C]

NM_014946.4(SPAST):c.1245+1G>C

Gene:

SPAST:spastin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p22.3

Genomic location:

Preferred name:

NM_014946.4(SPAST):c.1245+1G>C

HGVS:

NC_000002.12:g.32128480G>C
NG_008730.1:g.69870G>C
NM_001363823.2:c.1242+1G>C
NM_001363875.2:c.1146+1G>C
NM_001377959.1:c.1149+1G>C
NM_014946.4:c.1245+1G>CMANE SELECT
NM_199436.2:c.1149+1G>C
LRG_714:g.69870G>C
NC_000002.11:g.32353549G>C

Molecular consequence:

NM_001363823.2:c.1242+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001363875.2:c.1146+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001377959.1:c.1149+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_014946.4:c.1245+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_199436.2:c.1149+1G>C - 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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003524209	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11309678, 20562464, 22552817, 22960362, 26600529, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524209

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

germline

clinical testing

PubMed (6)
[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

Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations.

de Bot ST, van den Elzen RT, Mensenkamp AR, Schelhaas HJ, Willemsen MA, Knoers NV, Kremer HP, van de Warrenburg BP, Scheffer H.

J Neurol Neurosurg Psychiatry. 2010 Oct;81(10):1073-8. doi: 10.1136/jnnp.2009.201103. Epub 2010 Jun 20.

PubMed [citation]

PMID:: 20562464

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524209.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of 9, but is expected to preserve the integrity of the reading-frame (PMID: 11309678, 26600529). Disruption of this splice site has been observed in individuals with hereditary spastic paraplegia (HSP) (PMID: 11309678, 20562464, 22552817, 22960362, 26600529). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the SPAST gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened 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: Sep 29, 2024

ClinVar

Relating variation to medicine