NM_025137.4(SPG11):c.7325C>T (p.Ala2442Val) AND Hereditary spastic paraplegia 11

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 24, 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:: RCV002029365.3

Allele description [Variation Report for NM_025137.4(SPG11):c.7325C>T (p.Ala2442Val)]

NM_025137.4(SPG11):c.7325C>T (p.Ala2442Val)

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.7325C>T (p.Ala2442Val)

HGVS:

NC_000015.10:g.44563128G>A
NG_008885.1:g.105551C>T
NM_001160227.2:c.6986C>T
NM_025137.4:c.7325C>TMANE SELECT
NP_001153699.1:p.Ala2329Val
NP_079413.3:p.Ala2442Val
NC_000015.9:g.44855326G>A

Protein change:

A2329V

Links:

dbSNP: rs762374689

NCBI 1000 Genomes Browser:

rs762374689

Molecular consequence:

NM_001160227.2:c.6986C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_025137.4:c.7325C>T - 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

Recent activity

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RING-type domain-containing protein [Caenorhabditis elegans]
RING-type domain-containing protein [Caenorhabditis elegans]
gi|17505504|ref|NP_491737.1|

Protein
Zwei Ig domain protein zig-5 [Caenorhabditis elegans]
Zwei Ig domain protein zig-5 [Caenorhabditis elegans]
gi|71994240|ref|NP_499405.4|

Protein
Homo sapiens mRNA; cDNA DKFZp434H177 (from clone DKFZp434H177)
Homo sapiens mRNA; cDNA DKFZp434H177 (from clone DKFZp434H177)
gi|6453431|emb|AL133030.1|

Nucleotide
Caenorhabditis elegans ABC transporter domain-containing protein (wht-7), partia...
Caenorhabditis elegans ABC transporter domain-containing protein (wht-7), partial mRNA
gi|2220285924|ref|NM_001404165.1|

Nucleotide
F-box associated domain-containing protein [Caenorhabditis elegans]
F-box associated domain-containing protein [Caenorhabditis elegans]
gi|943463909|ref|NP_001303791.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002299156	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 24, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002299156

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 24, 2021)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV002299156.2

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2442 of the SPG11 protein (p.Ala2442Val). This variant is present in population databases (rs762374689, gnomAD 0.01%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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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