NM_003560.4(PLA2G6):c.916C>T (p.Arg306Trp) AND Infantile neuroaxonal dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 28, 2021
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:: RCV002023201.3

Allele description [Variation Report for NM_003560.4(PLA2G6):c.916C>T (p.Arg306Trp)]

NM_003560.4(PLA2G6):c.916C>T (p.Arg306Trp)

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.916C>T (p.Arg306Trp)

HGVS:

NC_000022.11:g.38132992G>A
NG_007094.3:g.86787C>T
NM_001004426.3:c.916C>T
NM_001199562.3:c.916C>T
NM_001349864.2:c.916C>T
NM_001349865.2:c.916C>T
NM_001349866.2:c.916C>T
NM_001349867.2:c.382C>T
NM_001349868.2:c.238C>T
NM_001349869.2:c.382C>T
NM_003560.4:c.916C>TMANE SELECT
NP_001004426.1:p.Arg306Trp
NP_001186491.1:p.Arg306Trp
NP_001336793.1:p.Arg306Trp
NP_001336794.1:p.Arg306Trp
NP_001336795.1:p.Arg306Trp
NP_001336796.1:p.Arg128Trp
NP_001336797.1:p.Arg80Trp
NP_001336798.1:p.Arg128Trp
NP_003551.2:p.Arg306Trp
LRG_1015t1:c.916C>T
LRG_1015:g.86787C>T
LRG_1015p1:p.Arg306Trp
NC_000022.10:g.38528999G>A
NG_007094.2:g.77699C>T

Protein change:

R128W

Links:

dbSNP: rs1301929071

NCBI 1000 Genomes Browser:

rs1301929071

Molecular consequence:

NM_001004426.3:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.916C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.382C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.238C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.382C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.916C>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
SCV002305313	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002305313

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 28, 2021)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002305313.2

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 306 of the PLA2G6 protein (p.Arg306Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PLA2G6-related conditions. 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. 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: Sep 29, 2024

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