NM_003560.4(PLA2G6):c.1904G>A (p.Arg635Gln) AND Infantile neuroaxonal dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV002513186.2

Allele description [Variation Report for NM_003560.4(PLA2G6):c.1904G>A (p.Arg635Gln)]

NM_003560.4(PLA2G6):c.1904G>A (p.Arg635Gln)

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.1904G>A (p.Arg635Gln)

Other names:

NM_003560.4(PLA2G6):c.1904G>A; p.Arg635Gln

HGVS:

NC_000022.11:g.38115657C>T
NG_007094.3:g.104122G>A
NG_033059.2:g.13G>A
NM_001004426.3:c.1742G>A
NM_001199562.3:c.1742G>A
NM_001349864.2:c.1904G>A
NM_001349865.2:c.1742G>A
NM_001349866.2:c.1742G>A
NM_001349867.2:c.1370G>A
NM_001349868.2:c.1226G>A
NM_001349869.2:c.1208G>A
NM_003560.4:c.1904G>AMANE SELECT
NP_001004426.1:p.Arg581Gln
NP_001186491.1:p.Arg581Gln
NP_001336793.1:p.Arg635Gln
NP_001336794.1:p.Arg581Gln
NP_001336795.1:p.Arg581Gln
NP_001336796.1:p.Arg457Gln
NP_001336797.1:p.Arg409Gln
NP_001336798.1:p.Arg403Gln
NP_003551.2:p.Arg635Gln
LRG_1015t1:c.1904G>A
LRG_1015:g.104122G>A
LRG_1015p1:p.Arg635Gln
NC_000022.10:g.38511664C>T
NC_000022.11:g.38115657C>T
NG_007094.2:g.95034G>A
NM_003560.2:c.1904G>A

Protein change:

R403Q; ARG635GLN

Links:

OMIM: 603604.0011; dbSNP: rs387906863

NCBI 1000 Genomes Browser:

rs387906863

Molecular consequence:

NM_001004426.3:c.1742G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.1742G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.1904G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.1742G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.1742G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.1370G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.1226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.1904G>A - 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
SCV003519119	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20938027, 32771225, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003519119

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

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

Phenotypic spectrum of patients with PLA2G6 mutation and PARK14-linked parkinsonism.

Yoshino H, Tomiyama H, Tachibana N, Ogaki K, Li Y, Funayama M, Hashimoto T, Takashima S, Hattori N.

Neurology. 2010 Oct 12;75(15):1356-61. doi: 10.1212/WNL.0b013e3181f73649.

PubMed [citation]

PMID:: 20938027

PLA2G6 variants associated with the number of affected alleles in Parkinson's disease in Japan.

Daida K, Nishioka K, Li Y, Yoshino H, Shimada T, Dougu N, Nakatsuji Y, Ohara S, Hashimoto T, Okiyama R, Yokochi F, Suzuki C, Tomiyama M, Kimura K, Ueda N, Tanaka F, Yamada H, Fujioka S, Tsuboi Y, Uozumi T, Takei T, Matsuzaki S, et al.

Neurobiol Aging. 2021 Jan;97:147.e1-147.e9. doi: 10.1016/j.neurobiolaging.2020.07.004. Epub 2020 Jul 13.

PubMed [citation]

PMID:: 32771225

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003519119.2

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 635 of the PLA2G6 protein (p.Arg635Gln). This variant is present in population databases (rs387906863, gnomAD 0.009%). This missense change has been observed in individuals with early onset Parkinson disease (PMID: 20938027, 32771225). ClinVar contains an entry for this variant (Variation ID: 30366). 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 with a positive predictive value of 80%. 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: May 26, 2024

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