NM_025137.4(SPG11):c.5249_5252del (p.Ser1750fs) AND Hereditary spastic paraplegia 11

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 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:: RCV003496202.2

Allele description [Variation Report for NM_025137.4(SPG11):c.5249_5252del (p.Ser1750fs)]

NM_025137.4(SPG11):c.5249_5252del (p.Ser1750fs)

Genes:

LOC130056971:ATAC-STARR-seq lymphoblastoid silent region 6398 [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.5249_5252del (p.Ser1750fs)

HGVS:

NC_000015.10:g.44584431_44584434del
NG_008885.1:g.84248_84251del
NG_191392.1:g.137_140del
NM_001160227.2:c.5249_5252del
NM_001411132.1:c.5122-17_5122-14del
NM_025137.4:c.5249_5252delMANE SELECT
NP_001153699.1:p.Ser1750fs
NP_079413.3:p.Ser1750fs
NC_000015.9:g.44876626_44876629del
NC_000015.9:g.44876629_44876632del

Protein change:

S1750fs

Molecular consequence:

NM_001160227.2:c.5249_5252del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_025137.4:c.5249_5252del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001411132.1:c.5122-17_5122-14del - intron variant - [Sequence Ontology: SO:0001627]

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

Recent activity

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JGI_XZT15212.rev NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7592486 3'...
JGI_XZT15212.rev NIH_XGC_tropTad5 Xenopus tropicalis cDNA clone IMAGE:7592486 3', mRNA sequence
gi|57062745|gnl|dbEST|26948137|gb|C 73.1|

Nucleotide
BX713849 XGC-tadpole Xenopus tropicalis cDNA clone TTpA015d11 3', mRNA sequence
BX713849 XGC-tadpole Xenopus tropicalis cDNA clone TTpA015d11 3', mRNA sequence
gi|38385251|gnl|dbEST|20429983|emb| 849.1|

Nucleotide
BJ086846 NIBB Mochii normalized Xenopus tailbud library Xenopus laevis cDNA clon...
BJ086846 NIBB Mochii normalized Xenopus tailbud library Xenopus laevis cDNA clone XL054h14 3', mRNA sequence
gi|17583410|gnl|dbEST|10555161|dbj| 846.1|

Nucleotide
AGENCOURT_36106164 NIH_XGC_tropKid1 Xenopus tropicalis cDNA clone IMAGE:7463933 ...
AGENCOURT_36106164 NIH_XGC_tropKid1 Xenopus tropicalis cDNA clone IMAGE:7463933 5', mRNA sequence
gi|55757014|gnl|dbEST|26391977|gb|C 43.1|

Nucleotide
5B7M Xenopus neurula plasmid library Xenopus laevis cDNA clone 5B7 5', mRNA sequ...
5B7M Xenopus neurula plasmid library Xenopus laevis cDNA clone 5B7 5', mRNA sequence
gi|3818767|gnl|dbEST|1770451|gb|AI0 .1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004368064	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19105190, 20110243, 22154821, 26556829, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004368064

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (5)
[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

Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

Denora PS, Schlesinger D, Casali C, Kok F, Tessa A, Boukhris A, Azzedine H, Dotti MT, Bruno C, Truchetto J, Biancheri R, Fedirko E, Di Rocco M, Bueno C, Malandrini A, Battini R, Sickl E, de Leva MF, Boespflug-Tanguy O, Silvestri G, Simonati A, Said E, et al.

Hum Mutat. 2009 Mar;30(3):E500-19. doi: 10.1002/humu.20945.

PubMed [citation]

PMID:: 19105190

SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.

Orlacchio A, Babalini C, Borreca A, Patrono C, Massa R, Basaran S, Munhoz RP, Rogaeva EA, St George-Hyslop PH, Bernardi G, Kawarai T.

Brain. 2010 Feb;133(Pt 2):591-8. doi: 10.1093/brain/awp325. Epub 2010 Jan 28.

PubMed [citation]

PMID:: 20110243
PMCID:: PMC2822627

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004368064.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ser1750Phefs*87) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. 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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