NM_025137.4(SPG11):c.6625C>T (p.Arg2209Cys) AND Spastic paraplegia 11, autosomal recessive

Clinical significance:Uncertain significance (Last evaluated: Dec 13, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000544170.4

Allele description [Variation Report for NM_025137.4(SPG11):c.6625C>T (p.Arg2209Cys)]

NM_025137.4(SPG11):c.6625C>T (p.Arg2209Cys)

Gene:
SPG11:SPG11 vesicle trafficking associated, spatacsin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q21.1
Genomic location:
Preferred name:
NM_025137.4(SPG11):c.6625C>T (p.Arg2209Cys)
HGVS:
  • NC_000015.10:g.44567553G>A
  • NG_008885.1:g.101126C>T
  • NM_001160227.2:c.6286C>T
  • NM_025137.4:c.6625C>TMANE SELECT
  • NP_001153699.1:p.Arg2096Cys
  • NP_079413.3:p.Arg2209Cys
  • NC_000015.9:g.44859751G>A
  • NM_025137.3:c.6625C>T
Protein change:
R2096C
Links:
dbSNP: rs374057859
NCBI 1000 Genomes Browser:
rs374057859
Molecular consequence:
  • NM_001160227.2:c.6286C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_025137.4:c.6625C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spastic paraplegia 11, autosomal recessive (SPG11)
Synonyms:
SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, COMPLICATED, WITH THIN CORPUS CALLOSUM; SPASTIC PARAPLEGIA, AUTOSOMAL RECESSIVE, WITH MENTAL IMPAIRMENT AND THIN CORPUS CALLOSUM; Spastic paraplegia 11; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011445; MedGen: C1858479; Orphanet: 2822; OMIM: 604360

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000642272Invitaecriteria provided, single submitter
Uncertain significance
(Dec 13, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000642272.4

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

Description

This sequence change replaces arginine with cysteine at codon 2209 of the SPG11 protein (p.Arg2209Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs374057859, ExAC 0.05%) but has not been reported in the literature in individuals with an SPG11-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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