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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

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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002139182Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 28, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 4, 2024