NM_020919.4(ALS2):c.3799dup (p.Ser1267fs) AND Infantile-onset ascending hereditary spastic paralysis

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 15, 2023
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:: RCV003613437.1

Allele description

NM_020919.4(ALS2):c.3799dup (p.Ser1267fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2q33.1

Genomic location:

Preferred name:

NM_020919.4(ALS2):c.3799dup (p.Ser1267fs)

HGVS:

NC_000002.12:g.201718114dup
NG_008775.1:g.68059dup
NM_001410975.1:c.3799dup
NM_020919.4:c.3799dupMANE SELECT
NP_001397904.1:p.Ser1267fs
NP_065970.2:p.Ser1267fs
LRG_654t1:c.3799dup
LRG_654:g.68059dup
LRG_654p1:p.Ser1267fs
NC_000002.11:g.202582836_202582837insT
NC_000002.11:g.202582837dup

Protein change:

S1267fs

Molecular consequence:

NM_001410975.1:c.3799dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_020919.4:c.3799dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004454661	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 15, 2023)	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

SCV004454661

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 15, 2023)

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, SCV004454661.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ALS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1267Lysfs*4) 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).

#	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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