NM_014363.6(SACS):c.8793del (p.Lys2931fs) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: May 20, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000706287.3

Allele description [Variation Report for NM_014363.6(SACS):c.8793del (p.Lys2931fs)]

NM_014363.6(SACS):c.8793del (p.Lys2931fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.8793del (p.Lys2931fs)
HGVS:
  • NC_000013.11:g.23335089del
  • NG_012342.1:g.103620del
  • NM_001278055.2:c.8352del
  • NM_014363.6:c.8793delMANE SELECT
  • NP_001264984.1:p.Lys2784fs
  • NP_055178.3:p.Lys2931fs
  • NC_000013.10:g.23909222del
  • NC_000013.10:g.23909228del
  • NM_014363.4:c.8793del
  • NM_014363.4:c.8793delA
  • NM_014363.5:c.8793del
  • NM_014363.5:c.8793delA
Protein change:
K2784fs
Links:
dbSNP: rs767871841
NCBI 1000 Genomes Browser:
rs767871841
Molecular consequence:
  • NM_001278055.2:c.8352del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.8793del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Spastic paraplegia
Synonyms:
Spastic paraplegia, lower limb
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000835327Invitaecriteria provided, single submitter
Pathogenic
(May 20, 2019)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sacsin-related autosomal recessive ataxia without prominent retinal myelinated fibers in Japan.

Hara K, Onodera O, Endo M, Kondo H, Shiota H, Miki K, Tanimoto N, Kimura T, Nishizawa M.

Mov Disord. 2005 Mar;20(3):380-2.

PubMed [citation]
PMID:
15486997

ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.

Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B.

Neurogenetics. 2008 Jul;9(3):207-14. doi: 10.1007/s10048-008-0131-7. Epub 2008 May 9. Erratum in: Neurogenetics. 2009 Feb;10(1):87.

PubMed [citation]
PMID:
18465152
PMCID:
PMC2441586
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000835327.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change results in a premature translational stop signal in the SACS gene (p.Lys2931Asnfs*22). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1649 amino acids (~36%) of the SACS protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with autosomal recessive spastic ataxia in a family (PMID: 15486997). This variant is also known as 6543delA in the literature. ClinVar contains an entry for this variant (Variation ID: 449517). A different truncation (p.Arg3636*) that lies downstream of this variant has been determined to be pathogenic (PMID: 18465152). This suggests that deletion of this region of the SACS protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 16, 2021

Support Center