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NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs) AND Hereditary spastic paraplegia

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 30, 2021
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:
RCV000824801.7

Allele description [Variation Report for NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs)]

NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs)

Gene:
SPG11:SPG11 vesicle trafficking associated, spatacsin [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_025137.4(SPG11):c.3711dup (p.Tyr1238fs)
Other names:
p.Tyr1238LeufsX27; p.Tyr1238Leufs*27
HGVS:
  • NC_000015.10:g.44598813dup
  • NG_008885.1:g.69867dup
  • NM_001160227.2:c.3711dup
  • NM_025137.4:c.3711dupMANE SELECT
  • NP_001153699.1:p.Tyr1238fs
  • NP_079413.3:p.Tyr1238fs
  • NC_000015.9:g.44891009_44891010insG
  • NC_000015.9:g.44891011dup
  • NM_025137.3:c.3711dup
  • NM_025137.3:c.3711dupC
Protein change:
Y1238fs
Links:
dbSNP: rs750663981
NCBI 1000 Genomes Browser:
rs750663981
Molecular consequence:
  • NM_001160227.2:c.3711dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_025137.4:c.3711dup - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Hereditary spastic paraplegia
Synonyms:
Familial spastic paraparesis
Identifiers:
MONDO: MONDO:0019064; MedGen: C0037773; OMIM: PS303350

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000712181Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Jun 16, 2016) 		germlineclinical testing

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

SCV002105708Genome Diagnostics Laboratory, The Hospital for Sick Children
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 30, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000712181.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.Tyr1238LeufsX27 variant in SPG11 has not been previously reported in the l iterature but it has been identified in 2/66,398 of chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org). Although this varian t has been seen in the general population, its frequency is low enough to be con sistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at positio n 1238 and leads to a premature termination codon 27 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. Biallel ic loss of function of the SPG11 gene is an established disease mechanism for sp astic paraplegia. In summary, this variant meets our criteria to be classified a s pathogenic for spastic paraplegia in an autosomal recessive manner based upon its predicted functional impact.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From Genome Diagnostics Laboratory, The Hospital for Sick Children, SCV002105708.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024