NM_014363.6(SACS):c.8542_8543del (p.Phe2848fs) AND Autosomal recessive spastic ataxia

Clinical significance:Pathogenic (Last evaluated: Aug 8, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000824756.1

Allele description [Variation Report for NM_014363.6(SACS):c.8542_8543del (p.Phe2848fs)]

NM_014363.6(SACS):c.8542_8543del (p.Phe2848fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.8542_8543del (p.Phe2848fs)
HGVS:
  • NC_000013.11:g.23335335_23335336del
  • NG_012342.1:g.103369_103370del
  • NM_001278055.2:c.8101_8102del
  • NM_014363.6:c.8542_8543delMANE SELECT
  • NP_001264984.1:p.Phe2701fs
  • NP_055178.3:p.Phe2848fs
  • NC_000013.10:g.23909472_23909473delAA
  • NC_000013.10:g.23909474_23909475del
  • NM_014363.4:c.8542_8543delTT
  • p.Phe2848ProfsX14
Protein change:
F2701fs
Links:
dbSNP: rs876657721
NCBI 1000 Genomes Browser:
rs876657721
Molecular consequence:
  • NM_001278055.2:c.8101_8102del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.8542_8543del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Autosomal recessive spastic ataxia
Identifiers:
MONDO: MONDO:0017847; MedGen: CN279276

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000271450Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Pathogenic
(Aug 8, 2015)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided21not providednot providednot providedclinical testing

Citations

PubMed

Mutations in SACS cause atypical and late-onset forms of ARSACS.

Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P.

Neurology. 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c.

PubMed [citation]
PMID:
20876471

Autosomal recessive spastic ataxia of Charlevoix-Saguenay: an overview.

Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F.

Parkinsonism Relat Disord. 2011 Jul;17(6):418-22. doi: 10.1016/j.parkreldis.2011.03.005. Epub 2011 Mar 30. Review.

PubMed [citation]
PMID:
21450511
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000271450.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (4)

Description

The p.Phe2848fs variant in SACS has not been previously reported in individuals with clinical features of autosomal recessive spastic ataxia of Charlevoix-Sague nay (ARSACS) or in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at positi on 2848 and leads to a premature termination codon 14 amino acids downstream. T his premature termination codon occurs within the last exon of the gene (exon 10 ), and is more likely to escape nonsense mediated decay (NMD). Therefore, this v ariant is predicted to result in a truncated protein that is 1718 amino acids sh orter and lacks several functional domains of the normal protein. Loss of functi on variants in the SACS gene, most of which occur in exon 10, have been reported in several patients with ARSACS (Bouhlal 2011), and animal models support a los s of function mechanism of disease (Lariviere 2015). In summary, this variant me ets our criteria to be classified as pathogenic for ARSACS in an autosomal reces sive manner (http://www.partners.org/personalizedmedicine/LMM).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided1not provided

Last Updated: Jul 7, 2021

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