NM_014363.6(SACS):c.8793del (p.Lys2931fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2024
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:: RCV000706287.9

Allele description [Variation Report for NM_014363.6(SACS):c.8793del (p.Lys2931fs)]

NM_014363.6(SACS):c.8793del (p.Lys2931fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.8793del (p.Lys2931fs)

HGVS:

NC_000013.11:g.23335089del
NG_012342.1:g.103620del
NM_001278055.2:c.8352del
NM_014363.6:c.8793delMANE SELECT
NP_001264984.1:p.Lys2784fs
NP_055178.3:p.Lys2931fs
NC_000013.10:g.23909222del
NC_000013.10:g.23909228del
NM_014363.4:c.8793del
NM_014363.4:c.8793delA
NM_014363.5:c.8793del
NM_014363.5:c.8793delA

Protein change:

K2784fs

Links:

dbSNP: rs767871841

NCBI 1000 Genomes Browser:

rs767871841

Molecular consequence:

NM_001278055.2:c.8352del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.8793del - 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
SCV000835327	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15486997, 18465152, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000835327

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2024)

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

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

ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.

Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B.

Neurogenetics. 2008 Jul;9(3):207-14. doi: 10.1007/s10048-008-0131-7. Epub 2008 May 9. Erratum in: Neurogenetics. 2009 Feb;10(1):87.

PubMed [citation]

PMID:: 18465152
PMCID:: PMC2441586

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000835327.6

#	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.Lys2931Asnfs*22) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1649 amino acid(s) of the SACS protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with autosomal recessive spastic ataxia (PMID: 15486997). It has also been observed to segregate with disease in related individuals. This variant is also known as 6543delA. ClinVar contains an entry for this variant (Variation ID: 449517). This variant disrupts a region of the SACS protein in which other variant(s) (p.Arg3636*) have been determined to be pathogenic (PMID: 18465152). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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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