NM_025137.4(SPG11):c.6451del (p.Ala2151fs) AND Hereditary spastic paraplegia 11

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 4, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000034245.13

Allele description [Variation Report for NM_025137.4(SPG11):c.6451del (p.Ala2151fs)]

NM_025137.4(SPG11):c.6451del (p.Ala2151fs)

Gene:

SPG11:SPG11 vesicle trafficking associated, spatacsin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_025137.4(SPG11):c.6451del (p.Ala2151fs)

HGVS:

NC_000015.10:g.44570552del
NG_008885.1:g.98128del
NM_001160227.2:c.6112del
NM_025137.4:c.6451delMANE SELECT
NP_001153699.1:p.Ala2038fs
NP_079413.3:p.Ala2151fs
NC_000015.9:g.44862749del
NC_000015.9:g.44862750del
NM_025137.3:c.6451delG

Protein change:

A2038fs

Links:

dbSNP: rs312262779

NCBI 1000 Genomes Browser:

rs312262779

Molecular consequence:

NM_001160227.2:c.6112del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_025137.4:c.6451del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary spastic paraplegia 11
Synonyms:: SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, COMPLICATED, WITH THIN CORPUS CALLOSUM; SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, WITH MENTAL IMPAIRMENT AND THIN CORPUS CALLOSUM; Spastic paraplegia 11, autosomal recessive; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011445; MedGen: C1858479; Orphanet: 2822; OMIM: 604360

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058185	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 17322883, 20301389
SCV000823620	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 4, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 17322883, 19105190, 20110243, 22154821, 26556829, 28492532
SCV002763708	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000058185

GeneReviews

no classification provided

not provided

unknown

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000823620

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 4, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002763708

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Spastic Paraplegia 11.

Stevanin G.

2008 Mar 27 [updated 2019 Dec 19]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301389

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, Denora PS, Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M, Fontaine B, Filla A, et al.

Nat Genet. 2007 Mar;39(3):366-72. Epub 2007 Feb 18.

PubMed [citation]

PMID:: 17322883

See all PubMed Citations (8)

Details of each submission

From GeneReviews, SCV000058185.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000823620.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant is present in population databases (rs312262779, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 41344). This premature translational stop signal has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 17322883). It has also been observed to segregate with disease in related individuals. This sequence change creates a premature translational stop signal (p.Ala2151Profs*22) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829).

#	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

From Genome-Nilou Lab, SCV002763708.1

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

#	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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