NM_003560.4(PLA2G6):c.1771C>T (p.Arg591Trp) AND Infantile neuroaxonal dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 28, 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:: RCV002032692.6

Allele description [Variation Report for NM_003560.4(PLA2G6):c.1771C>T (p.Arg591Trp)]

NM_003560.4(PLA2G6):c.1771C>T (p.Arg591Trp)

Gene:

PLA2G6:phospholipase A2 group VI [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_003560.4(PLA2G6):c.1771C>T (p.Arg591Trp)

Other names:

NM_003560.4(PLA2G6):c.1771C>T; p.Arg591Trp

HGVS:

NC_000022.11:g.38116183G>A
NG_007094.3:g.103596C>T
NM_001004426.3:c.1609C>T
NM_001199562.3:c.1609C>T
NM_001349864.2:c.1771C>T
NM_001349865.2:c.1609C>T
NM_001349866.2:c.1609C>T
NM_001349867.2:c.1237C>T
NM_001349868.2:c.1093C>T
NM_001349869.2:c.1075C>T
NM_003560.4:c.1771C>TMANE SELECT
NP_001004426.1:p.Arg537Trp
NP_001186491.1:p.Arg537Trp
NP_001336793.1:p.Arg591Trp
NP_001336794.1:p.Arg537Trp
NP_001336795.1:p.Arg537Trp
NP_001336796.1:p.Arg413Trp
NP_001336797.1:p.Arg365Trp
NP_001336798.1:p.Arg359Trp
NP_003551.2:p.Arg591Trp
LRG_1015t1:c.1771C>T
LRG_1015:g.103596C>T
LRG_1015p1:p.Arg591Trp
NC_000022.10:g.38512190G>A
NG_007094.2:g.94508C>T

Protein change:

R359W

Links:

dbSNP: rs1043378899

NCBI 1000 Genomes Browser:

rs1043378899

Molecular consequence:

NM_001004426.3:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.1771C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.1609C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.1237C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.1093C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.1075C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.1771C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Infantile neuroaxonal dystrophy (NBIA2A)
Synonyms:: NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A; Seitelberger disease; Infantile neuroaxonal dystrophy 1
Identifiers:: MONDO: MONDO:0024457; MedGen: C0270724; Orphanet: 35069; OMIM: 256600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002139182	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 28, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19138334, 27882168, 34272103, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002139182

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 28, 2023)

germline

clinical testing

PubMed (4)
[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

Clinical study and PLA2G6 mutation screening analysis in Chinese patients with infantile neuroaxonal dystrophy.

Wu Y, Jiang Y, Gao Z, Wang J, Yuan Y, Xiong H, Chang X, Bao X, Zhang Y, Xiao J, Wu X.

Eur J Neurol. 2009 Feb;16(2):240-5. doi: 10.1111/j.1468-1331.2008.02397.x. Epub 2008 Dec 9.

PubMed [citation]

PMID:: 19138334

Monozygotic twins with infantile neuroaxonal dystrophy: A case report and literature review.

Li H, Zou Y, Bao X, Wang H, Wang J, Jin H, Che Y, Tang X.

Exp Ther Med. 2016 Nov;12(5):3387-3389. Epub 2016 Sep 30.

PubMed [citation]

PMID:: 27882168
PMCID:: PMC5103811

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002139182.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 591 of the PLA2G6 protein (p.Arg591Trp). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individuals with PLA2G6-related conditions (PMID: 19138334, 27882168, 34272103). ClinVar contains an entry for this variant (Variation ID: 1298894). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLA2G6 protein function. 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: Aug 4, 2024

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