NM_003560.4(PLA2G6):c.901C>T (p.Arg301Cys) AND Infantile neuroaxonal dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 6, 2022
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:: RCV001858869.3

Allele description [Variation Report for NM_003560.4(PLA2G6):c.901C>T (p.Arg301Cys)]

NM_003560.4(PLA2G6):c.901C>T (p.Arg301Cys)

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.901C>T (p.Arg301Cys)

HGVS:

NC_000022.11:g.38133007G>A
NG_007094.3:g.86772C>T
NM_001004426.3:c.901C>T
NM_001199562.3:c.901C>T
NM_001349864.2:c.901C>T
NM_001349865.2:c.901C>T
NM_001349866.2:c.901C>T
NM_001349867.2:c.367C>T
NM_001349868.2:c.223C>T
NM_001349869.2:c.367C>T
NM_003560.4:c.901C>TMANE SELECT
NP_001004426.1:p.Arg301Cys
NP_001186491.1:p.Arg301Cys
NP_001336793.1:p.Arg301Cys
NP_001336794.1:p.Arg301Cys
NP_001336795.1:p.Arg301Cys
NP_001336796.1:p.Arg123Cys
NP_001336797.1:p.Arg75Cys
NP_001336798.1:p.Arg123Cys
NP_003551.2:p.Arg301Cys
LRG_1015t1:c.901C>T
LRG_1015:g.86772C>T
LRG_1015p1:p.Arg301Cys
NC_000022.10:g.38529014G>A
NC_000022.10:g.38529014G>A
NG_007094.2:g.77684C>T
NM_003560.2:c.901C>T

Protein change:

R123C

Links:

dbSNP: rs367854265

NCBI 1000 Genomes Browser:

rs367854265

Molecular consequence:

NM_001004426.3:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.901C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.367C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.223C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.367C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.901C>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
SCV002270991	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 6, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21368765, 32771225, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002270991

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 6, 2022)

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

PLA2G6 variant in Parkinson's disease.

Tomiyama H, Yoshino H, Ogaki K, Li L, Yamashita C, Li Y, Funayama M, Sasaki R, Kokubo Y, Kuzuhara S, Hattori N.

J Hum Genet. 2011 May;56(5):401-3. doi: 10.1038/jhg.2011.22. Epub 2011 Mar 3.

PubMed [citation]

PMID:: 21368765

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, SCV002270991.2

#	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 cysteine, which is neutral and slightly polar, at codon 301 of the PLA2G6 protein (p.Arg301Cys). This variant is present in population databases (rs367854265, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of PLA2G6-related conditions (PMID: 21368765, 32771225). ClinVar contains an entry for this variant (Variation ID: 809369). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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: Jun 17, 2024

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