NM_014363.6(SACS):c.7655dup (p.Asn2552fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 27, 2019
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:: RCV001213960.8

Allele description [Variation Report for NM_014363.6(SACS):c.7655dup (p.Asn2552fs)]

NM_014363.6(SACS):c.7655dup (p.Asn2552fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.7655dup (p.Asn2552fs)

HGVS:

NC_000013.11:g.23336224dup
NG_012342.1:g.102482dup
NM_001278055.2:c.7214dup
NM_014363.6:c.7655dupMANE SELECT
NP_001264984.1:p.Asn2405fs
NP_055178.3:p.Asn2552fs
NC_000013.10:g.23910359_23910360insT
NC_000013.10:g.23910363dup
NM_014363.5:c.7655dup

Protein change:

N2405fs

Links:

dbSNP: rs1868578034

NCBI 1000 Genomes Browser:

rs1868578034

Molecular consequence:

NM_001278055.2:c.7214dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.7655dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

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long-chain-fatty-acid--CoA ligase ACSBG2 [Camelus ferus]
long-chain-fatty-acid--CoA ligase ACSBG2 [Camelus ferus]
gi|1811029393|ref|XP_032322225.1|

Protein
Olea europaea cultivar:Leccino, Donna Francesca, Oliva Rossa, Cellina
Olea europaea cultivar:Leccino, Donna Francesca, Oliva Rossa, Cellina
Comparative transcriptome analysis of four olive cultivars in response to infection by Xylella fastidiosa

BioProject
Colony-Stimulating Factors
Colony-Stimulating Factors
Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies...<br/>Year introduced: 1979(1976)

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001385622	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 27, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15486997, 19892370, 21745802, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001385622

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 27, 2019)

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

Hara K, Onodera O, Endo M, Kondo H, Shiota H, Miki K, Tanimoto N, Kimura T, Nishizawa M.

Mov Disord. 2005 Mar;20(3):380-2.

PubMed [citation]

PMID:: 15486997

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001385622.5

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SACS protein. Other variant(s) that disrupt this region (p.Lys2931Asnfs*22 and p.Arg3903*) have been determined to be pathogenic (PMID: 15486997, 19892370, 21745802). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with SACS-related conditions. This sequence change results in a premature translational stop signal in the SACS gene (p.Asn2552Lysfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2028 amino acids of the SACS protein.

#	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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