NM_020919.4(ALS2):c.116G>A (p.Gly39Glu) AND Infantile-onset ascending hereditary spastic paralysis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 9, 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:: RCV002051336.4

Allele description [Variation Report for NM_020919.4(ALS2):c.116G>A (p.Gly39Glu)]

NM_020919.4(ALS2):c.116G>A (p.Gly39Glu)

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.116G>A (p.Gly39Glu)

HGVS:

NC_000002.12:g.201767288C>T
NG_008775.1:g.18885G>A
NM_001135745.2:c.116G>A
NM_020919.4:c.116G>AMANE SELECT
NP_001129217.1:p.Gly39Glu
NP_065970.2:p.Gly39Glu
LRG_654t1:c.116G>A
LRG_654:g.18885G>A
LRG_654p1:p.Gly39Glu
NC_000002.11:g.202632011C>T

Protein change:

G39E

Links:

dbSNP: rs2106102393

NCBI 1000 Genomes Browser:

rs2106102393

Molecular consequence:

NM_001135745.2:c.116G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020919.4:c.116G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002110951	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 9, 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

SCV002110951

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 9, 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, SCV002110951.3

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

Description

This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ALS2-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 39 of the ALS2 protein (p.Gly39Glu).

#	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

ClinVar

Relating variation to medicine