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NM_025137.4(SPG11):c.5462G>A (p.Arg1821Lys) AND Hereditary spastic paraplegia 11

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 29, 2021
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:
RCV000795161.4

Allele description [Variation Report for NM_025137.4(SPG11):c.5462G>A (p.Arg1821Lys)]

NM_025137.4(SPG11):c.5462G>A (p.Arg1821Lys)

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.5462G>A (p.Arg1821Lys)
HGVS:
  • NC_000015.10:g.44584218C>T
  • NG_008885.1:g.84461G>A
  • NM_001160227.2:c.5462G>A
  • NM_025137.4:c.5462G>AMANE SELECT
  • NP_001153699.1:p.Arg1821Lys
  • NP_079413.3:p.Arg1821Lys
  • NC_000015.9:g.44876416C>T
  • NM_025137.3:c.5462G>A
Protein change:
R1821K
Links:
dbSNP: rs777449266
NCBI 1000 Genomes Browser:
rs777449266
Molecular consequence:
  • NM_001160227.2:c.5462G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_025137.4:c.5462G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000934604Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 29, 2021) 		germlineclinical testing

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

Help

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000934604.3

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

Description

This sequence change replaces arginine with lysine at codon 1821 of the SPG11 protein (p.Arg1821Lys). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and lysine. This variant is present in population databases (rs777449266, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. 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: Sep 29, 2024