NC_000002.11:g.(?_202501451)_(202633608_?)del AND Infantile-onset ascending hereditary spastic paralysis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 4, 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:: RCV003105409.4

Allele description [Variation Report for NC_000002.11:g.(?_202501451)_(202633608_?)del]

NC_000002.11:g.(?_202501451)_(202633608_?)del

Genes:: MPP4:MAGUK p55 scaffold protein 4 [Gene - OMIM - HGNC]
ALS2:alsin Rho guanine nucleotide exchange factor ALS2 [Gene - OMIM - HGNC]
TMEM237:transmembrane protein 237 [Gene - OMIM - HGNC]
Variant type:: Deletion
Cytogenetic location:: 2q33.1
Genomic location:: Chr2: 202501451 - 202633608 (on Assembly GRCh37)
Preferred name:: NC_000002.11:g.(?_202501451)_(202633608_?)del
HGVS:: NC_000002.11:g.(?_202501451)_(202633608_?)del
This HGVS expression did not pass validation

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
SCV003791776	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 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

SCV003791776

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003791776.3

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

Description

A gross deletion of the genomic region encompassing the full coding sequence of the ALS2 gene has been identified. Loss-of-function variants in ALS2 are known to be pathogenic (PMID: 11586298, 24315819). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. 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: Sep 29, 2024

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