NM_014363.6(SACS):c.7764_7767dup (p.Val2590fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 27, 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:: RCV001046076.8

Allele description [Variation Report for NM_014363.6(SACS):c.7764_7767dup (p.Val2590fs)]

NM_014363.6(SACS):c.7764_7767dup (p.Val2590fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.7764_7767dup (p.Val2590fs)

HGVS:

NC_000013.11:g.23336110_23336113dup
NG_012342.1:g.102591_102594dup
NM_001278055.2:c.7323_7326dup
NM_014363.6:c.7764_7767dupMANE SELECT
NP_001264984.1:p.Val2443fs
NP_055178.3:p.Val2590fs
NC_000013.10:g.23910247_23910248insACAA
NC_000013.10:g.23910249_23910252dup
NM_014363.5:c.7764_7767dup

Protein change:

V2443fs

Links:

dbSNP: rs1868567420

NCBI 1000 Genomes Browser:

rs1868567420

Molecular consequence:

NM_001278055.2:c.7323_7326dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.7764_7767dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001209962	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 27, 2023)	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

SCV001209962

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 27, 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

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, SCV001209962.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SACS protein in which other variant(s) (p.Lys2931Asnfs*22, p.Arg3903*) have been determined to be pathogenic (PMID: 15486997, 19892370, 21745802). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 843447). 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.Val2590Leufs*12) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1990 amino acid(s) 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

ClinVar

Relating variation to medicine