NM_014363.6(SACS):c.2439_2440del (p.Val815fs) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: May 3, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001382654.1

Allele description [Variation Report for NM_014363.6(SACS):c.2439_2440del (p.Val815fs)]

NM_014363.6(SACS):c.2439_2440del (p.Val815fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.2439_2440del (p.Val815fs)
HGVS:
  • NC_000013.11:g.23341436_23341437del
  • NG_012342.1:g.97266_97267del
  • NM_001278055.2:c.1998_1999del
  • NM_014363.6:c.2439_2440delMANE SELECT
  • NP_001264984.1:p.Val668fs
  • NP_055178.3:p.Val815fs
  • NC_000013.10:g.23915575_23915576del
  • NM_014363.4:c.2439_2440del
  • NM_014363.4:c.2439_2440delAT
  • NM_014363.6:c.2439_2440delATMANE SELECT
Protein change:
V668fs
Links:
dbSNP: rs775059063
NCBI 1000 Genomes Browser:
rs775059063
Molecular consequence:
  • NM_001278055.2:c.1998_1999del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.2439_2440del - frameshift variant - [Sequence Ontology: SO:0001589]
Functional consequence:
No function

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001581541Invitaecriteria provided, single submitter
Pathogenic
(May 3, 2020)
germlineclinical testing

PubMed (4)
[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

Exome sequencing: an efficient diagnostic tool for complex neurodegenerative disorders.

Hammer MB, Eleuch-Fayache G, Gibbs JR, Arepalli SK, Chong SB, Sassi C, Bouhlal Y, Hentati F, Amouri R, Singleton AB.

Eur J Neurol. 2013 Mar;20(3):486-492. doi: 10.1111/j.1468-1331.2012.03883.x. Epub 2012 Oct 9.

PubMed [citation]
PMID:
23043354
PMCID:
PMC4669564

Novel mutations in the sacsin gene in ataxia patients from Maritime Canada.

Guernsey DL, Dubé MP, Jiang H, Asselin G, Blowers S, Evans S, Ferguson M, Macgillivray C, Matsuoka M, Nightingale M, Rideout A, Delatycki M, Orr A, Ludman M, Dooley J, Riddell C, Samuels ME.

J Neurol Sci. 2010 Jan 15;288(1-2):79-87. doi: 10.1016/j.jns.2009.09.034. Epub 2009 Nov 4.

PubMed [citation]
PMID:
19892370
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001581541.1

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

Description

This sequence change results in a premature translational stop signal in the SACS gene (p.Val815Glyfs*4). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3765 amino acids of the SACS protein. This variant is present in population databases (rs775059063, ExAC 0.01%). This variant has been observed in individual(s) with spastic ataxia of Charlevoix-Saguenay (PMID: 23043354). ClinVar contains an entry for this variant (Variation ID: 188856). This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Arg3903* and p.Leu4303*) have been determined to be pathogenic (PMID: 19892370, 21745802, Invitae). This suggests that variants that disrupt this region of the protein are likely to be 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

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