NM_014363.6(SACS):c.7504C>T (p.Arg2502Ter) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 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:: RCV001851681.8

Allele description [Variation Report for NM_014363.6(SACS):c.7504C>T (p.Arg2502Ter)]

NM_014363.6(SACS):c.7504C>T (p.Arg2502Ter)

Gene:

SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.7504C>T (p.Arg2502Ter)

Other names:

5254C>T

HGVS:

NC_000013.11:g.23336372G>A
NG_012342.1:g.102331C>T
NM_001278055.2:c.7063C>T
NM_014363.6:c.7504C>TMANE SELECT
NP_001264984.1:p.Arg2355Ter
NP_055178.3:p.Arg2502Ter
NC_000013.10:g.23910511G>A
NM_014363.4:c.7504C>T
NM_014363.5:c.7504C>T
c.5254C>T

Nucleotide change:

5254C-T

Protein change:

R2355*

Links:

OMIM: 604490.0002; dbSNP: rs281865118

Molecular consequence:

NM_001278055.2:c.7063C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_014363.6:c.7504C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002124857	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10655055, 30901567, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002124857

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B, Bouchard JP, Mathieu J, Melançon SB, Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A.

Nat Genet. 2000 Feb;24(2):120-5.

PubMed [citation]

PMID:: 10655055

Expanding the clinical description of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Briand MM, Rodrigue X, Lessard I, Mathieu J, Brais B, Côté I, Gagnon C.

J Neurol Sci. 2019 May 15;400:39-41. doi: 10.1016/j.jns.2019.03.008. Epub 2019 Mar 12.

PubMed [citation]

PMID:: 30901567

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002124857.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg2502*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2078 amino acid(s) of the SACS protein. This variant is present in population databases (rs281865118, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with autosomal recessive spastic ataxia of Charlevoix-Saguenay (PMID: 10655055, 30901567). This variant is also known as g.5254C>T. ClinVar contains an entry for this variant (Variation ID: 5513). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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