NM_014363.6(SACS):c.8807del (p.Gly2936fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 3, 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:: RCV003588926.2

Allele description [Variation Report for NM_014363.6(SACS):c.8807del (p.Gly2936fs)]

NM_014363.6(SACS):c.8807del (p.Gly2936fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.8807del (p.Gly2936fs)

HGVS:

NC_000013.11:g.23335070del
NG_012342.1:g.103634del
NM_001278055.2:c.8366del
NM_014363.6:c.8807delMANE SELECT
NP_001264984.1:p.Gly2789fs
NP_055178.3:p.Gly2936fs
NC_000013.10:g.23909208del
NC_000013.10:g.23909209del

Protein change:

G2789fs

Molecular consequence:

NM_001278055.2:c.8366del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.8807del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004294598	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10655055, 11788093, 22307627, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294598

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 3, 2023)

germline

clinical testing

PubMed (4)
[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

Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Mercier J, Prévost C, Engert JC, Bouchard JP, Mathieu J, Richter A.

Genet Test. 2001 Fall;5(3):255-9.

PubMed [citation]

PMID:: 11788093

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004294598.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant disrupts a region of the SACS protein in which other variant(s) (p.Ile2949Phefs*4) have been determined to be pathogenic (PMID: 10655055, 11788093, 22307627). 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.Gly2936Valfs*17) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1644 amino acid(s) of the SACS protein. 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: Sep 29, 2024

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