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NM_014946.4(SPAST):c.1173+2dup AND Hereditary spastic paraplegia 4

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 18, 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:
RCV003525268.2

Allele description [Variation Report for NM_014946.4(SPAST):c.1173+2dup]

NM_014946.4(SPAST):c.1173+2dup

Gene:
SPAST:spastin [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p22.3
Genomic location:
Preferred name:
NM_014946.4(SPAST):c.1173+2dup
HGVS:
  • NC_000002.12:g.32127024dup
  • NG_008730.1:g.68414dup
  • NM_001363823.2:c.1170+2dup
  • NM_001363875.2:c.1074+2dup
  • NM_001377959.1:c.1077+2dup
  • NM_014946.4:c.1173+2dupMANE SELECT
  • NM_199436.2:c.1077+2dup
  • LRG_714:g.68414dup
  • NC_000002.11:g.32352092_32352093insT
  • NC_000002.11:g.32352093dup
Molecular consequence:
  • NM_001363823.2:c.1170+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001363875.2:c.1074+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001377959.1:c.1077+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_014946.4:c.1173+2dup - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_199436.2:c.1077+2dup - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004292421Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 18, 2023) 		germlineclinical testing

PubMed (4)
[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

SPAST mutation spectrum and familial occurrence among Czech patients with pure hereditary spastic paraplegia.

Mészárosová AU, Putzová M, Čermáková M, Vávrová D, Doležalová K, Smetanová I, Stejskal D, Beetz C, Seeman P.

J Hum Genet. 2016 Oct;61(10):845-850. doi: 10.1038/jhg.2016.73. Epub 2016 Jun 23.

PubMed [citation]
PMID:
27334366

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292421.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change falls in intron 8 of the SPAST gene. It does not directly change the encoded amino acid sequence of the SPAST protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with SPAST-related conditions (PMID: 27334366; Invitae). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024