NM_020919.4(ALS2):c.4528C>T (p.Arg1510Ter) AND Infantile-onset ascending hereditary spastic paralysis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 17, 2022
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:: RCV001992862.3

Allele description [Variation Report for NM_020919.4(ALS2):c.4528C>T (p.Arg1510Ter)]

NM_020919.4(ALS2):c.4528C>T (p.Arg1510Ter)

Gene:

ALS2:alsin Rho guanine nucleotide exchange factor ALS2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

NM_020919.4(ALS2):c.4528C>T (p.Arg1510Ter)

HGVS:

NC_000002.12:g.201706898G>A
NG_008775.1:g.79275C>T
NM_020919.4:c.4528C>TMANE SELECT
NP_065970.2:p.Arg1510Ter
LRG_654t1:c.4528C>T
LRG_654:g.79275C>T
LRG_654p1:p.Arg1510Ter
NC_000002.11:g.202571621G>A

Protein change:

R1510*

Links:

dbSNP: rs1391892163

NCBI 1000 Genomes Browser:

rs1391892163

Molecular consequence:

NM_020919.4:c.4528C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Infantile-onset ascending hereditary spastic paralysis (IAHSP)
Synonyms:: Spastic paralysis, infantile onset ascending; Autosomal Recessive Juvenile Amyotrophic Lateral Sclerosis
Identifiers:: MONDO: MONDO:0011797; MedGen: C2931441; Orphanet: 293168; OMIM: 607225

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002219361	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11586298, 24315819, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002219361

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 2022)

germline

clinical testing

PubMed (3)
[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

A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2.

Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, Miyamoto N, Showguchi-Miyata J, Okada Y, Singaraja R, Figlewicz DA, Kwiatkowski T, Hosler BA, Sagie T, Skaug J, Nasir J, Brown RH Jr, Scherer SW, Rouleau GA, Hayden MR, Ikeda JE.

Nat Genet. 2001 Oct;29(2):166-73.

PubMed [citation]

PMID:: 11586298

Infantile-onset ascending hereditary spastic paraplegia with bulbar involvement due to the novel ALS2 mutation c.2761C>T.

Wakil SM, Ramzan K, Abuthuraya R, Hagos S, Al-Dossari H, Al-Omar R, Murad H, Chedrawi A, Al-Hassnan ZN, Finsterer J, Bohlega S.

Gene. 2014 Feb 15;536(1):217-20. doi: 10.1016/j.gene.2013.11.043. Epub 2013 Dec 4.

PubMed [citation]

PMID:: 24315819

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV002219361.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg1510*) in the ALS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALS2 are known to be pathogenic (PMID: 11586298, 24315819). This variant has not been reported in the literature in individuals affected with ALS2-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: Feb 28, 2024

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