NM_025137.4(SPG11):c.6811_6812del (p.Leu2271fs) AND Hereditary spastic paraplegia 11

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 2, 2022
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:: RCV002570637.3

Allele description

NM_025137.4(SPG11):c.6811_6812del (p.Leu2271fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

15q21.1

Genomic location:

Preferred name:

NM_025137.4(SPG11):c.6811_6812del (p.Leu2271fs)

HGVS:

NC_000015.10:g.44566248AG[1]
NG_008885.1:g.102428CT[1]
NM_001160227.2:c.6472_6473del
NM_025137.4:c.6811_6812delMANE SELECT
NP_001153699.1:p.Leu2158fs
NP_079413.3:p.Leu2271fs
NC_000015.9:g.44858446AG[1]
NC_000015.9:g.44858446_44858447del
NM_025137.4:c.6811_6812delCTMANE SELECT

Protein change:

L2158fs

Links:

dbSNP: rs1268815918

NCBI 1000 Genomes Browser:

rs1268815918

Molecular consequence:

NM_001160227.2:c.6472_6473del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_025137.4:c.6811_6812del - 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
SCV003461888	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 24833714, 29877287, 19105190, 20110243, 22154821, 26556829, 28492532
SCV004046788	Institute of Human Genetics, University Hospital of Duesseldorf	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	not provided	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003461888

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004046788

Institute of Human Genetics, University Hospital of Duesseldorf

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

not provided

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	germline	yes	not provided	not provided	not provided	not provided	not provided	not provided
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48.

Pensato V, Castellotti B, Gellera C, Pareyson D, Ciano C, Nanetti L, Salsano E, Piscosquito G, Sarto E, Eoli M, Moroni I, Soliveri P, Lamperti E, Chiapparini L, Di Bella D, Taroni F, Mariotti C.

Brain. 2014 Jul;137(Pt 7):1907-20. doi: 10.1093/brain/awu121. Epub 2014 May 15.

PubMed [citation]

PMID:: 24833714

Novel SPG11 Mutations in a Patient with Symptoms Mimicking Multiple Sclerosis.

Mukai M, Koh K, Ohnuki Y, Nagata E, Takiyama Y, Takizawa S.

Intern Med. 2018 Nov 1;57(21):3183-3186. doi: 10.2169/internalmedicine.0976-18. Epub 2018 Jun 6.

PubMed [citation]

PMID:: 29877287
PMCID:: PMC6262711

See all PubMed Citations (8)

Details of each submission

From Invitae, SCV003461888.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.6809_6810delCT. This premature translational stop signal has been observed in individual(s) with SPG11-related conditions (PMID: 24833714, 29877287). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu2271Aspfs*68) 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 Institute of Human Genetics, University Hospital of Duesseldorf, SCV004046788.1

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

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

Last Updated: Feb 20, 2024

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