NM_003560.4(PLA2G6):c.991G>A (p.Asp331Asn) AND Infantile neuroaxonal dystrophy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000626136.13

Allele description [Variation Report for NM_003560.4(PLA2G6):c.991G>A (p.Asp331Asn)]

NM_003560.4(PLA2G6):c.991G>A (p.Asp331Asn)

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.991G>A (p.Asp331Asn)

Other names:

NM_003560.4(PLA2G6):c.991G>A; p.Asp331Asn

HGVS:

NC_000022.11:g.38132917C>T
NG_007094.3:g.86862G>A
NM_001004426.3:c.991G>A
NM_001199562.3:c.991G>A
NM_001349864.2:c.991G>A
NM_001349865.2:c.991G>A
NM_001349866.2:c.991G>A
NM_001349867.2:c.457G>A
NM_001349868.2:c.313G>A
NM_001349869.2:c.457G>A
NM_003560.4:c.991G>AMANE SELECT
NP_001004426.1:p.Asp331Asn
NP_001186491.1:p.Asp331Asn
NP_001336793.1:p.Asp331Asn
NP_001336794.1:p.Asp331Asn
NP_001336795.1:p.Asp331Asn
NP_001336796.1:p.Asp153Asn
NP_001336797.1:p.Asp105Asn
NP_001336798.1:p.Asp153Asn
NP_003551.2:p.Asp331Asn
LRG_1015t1:c.991G>A
LRG_1015:g.86862G>A
LRG_1015p1:p.Asp331Asn
NC_000022.10:g.38528924C>T
NG_007094.2:g.77774G>A
NM_003560.2:c.991G>A
NM_003560.3:c.991G>A

Protein change:

D105N

Links:

dbSNP: rs199935023

NCBI 1000 Genomes Browser:

rs199935023

Molecular consequence:

NM_001004426.3:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.991G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.313G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.991G>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
SCV000746766	Genomic Research Center, Shahid Beheshti University of Medical Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 30, 2023)	inherited	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000826955	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21368765, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000746766

Genomic Research Center, Shahid Beheshti University of Medical Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 30, 2023)

inherited

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000826955

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2021)

germline

clinical testing

PubMed (2)
[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	inherited	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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

See all PubMed Citations (3)

Details of each submission

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000746766.3

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000826955.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid with asparagine at codon 331 of the PLA2G6 protein (p.Asp331Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs199935023, ExAC 0.01%). This missense change has been observed in individual(s) with Parkinson disease (PMID: 21368765). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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: Oct 20, 2024

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