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NM_014363.6(SACS):c.7316_7320del (p.Lys2439fs) AND Spastic paraplegia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 31, 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:
RCV001962960.4

Allele description [Variation Report for NM_014363.6(SACS):c.7316_7320del (p.Lys2439fs)]

NM_014363.6(SACS):c.7316_7320del (p.Lys2439fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.7316_7320del (p.Lys2439fs)
HGVS:
  • NC_000013.11:g.23336556TTTCT[1]
  • NG_012342.1:g.102138AGAAA[1]
  • NM_001278055.2:c.6875_6879del
  • NM_014363.6:c.7316_7320delMANE SELECT
  • NP_001264984.1:p.Lys2292fs
  • NP_055178.3:p.Lys2439fs
  • NC_000013.10:g.23910695TTTCT[1]
  • NC_000013.10:g.23910695_23910699del
Protein change:
K2292fs
Links:
dbSNP: rs2137601578
NCBI 1000 Genomes Browser:
rs2137601578
Molecular consequence:
  • NM_001278055.2:c.6875_6879del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.7316_7320del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Spastic paraplegia
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002228230Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 31, 2022) 		germlineclinical testing

PubMed (3)
[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

Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey.

Richter AM, Ozgul RK, Poisson VC, Topaloglu H.

Neurogenetics. 2004 Sep;5(3):165-70. Epub 2004 May 20.

PubMed [citation]
PMID:
15156359

Structural basis of defects in the sacsin HEPN domain responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Kozlov G, Denisov AY, Girard M, Dicaire MJ, Hamlin J, McPherson PS, Brais B, Gehring K.

J Biol Chem. 2011 Jun 10;286(23):20407-12. doi: 10.1074/jbc.M111.232884. Epub 2011 Apr 20.

PubMed [citation]
PMID:
21507954
PMCID:
PMC3121481
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002228230.3

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

Description

This variant disrupts a region of the SACS protein in which other variant(s) (p.Tyr4538*) have been determined to be pathogenic (PMID: 15156359, 21507954). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys2439Thrfs*5) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2141 amino acid(s) of the SACS protein. 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: Sep 29, 2024