NM_003560.4(PLA2G6):c.2129G>A (p.Arg710His) AND Infantile neuroaxonal dystrophy

Clinical significance:Uncertain significance (Last evaluated: Dec 20, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000804046.1

Allele description [Variation Report for NM_003560.4(PLA2G6):c.2129G>A (p.Arg710His)]

NM_003560.4(PLA2G6):c.2129G>A (p.Arg710His)

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.2129G>A (p.Arg710His)
HGVS:
  • NC_000022.11:g.38113560C>T
  • NG_007094.2:g.97131G>A
  • NG_007094.3:g.106219G>A
  • NG_033059.2:g.2110G>A
  • NM_001004426.3:c.1967G>A
  • NM_001199562.3:c.1967G>A
  • NM_001349864.2:c.2129G>A
  • NM_001349865.2:c.1967G>A
  • NM_001349866.2:c.1967G>A
  • NM_001349867.2:c.1595G>A
  • NM_001349868.2:c.1451G>A
  • NM_001349869.2:c.1433G>A
  • NM_003560.4:c.2129G>AMANE SELECT
  • NP_001004426.1:p.Arg656His
  • NP_001186491.1:p.Arg656His
  • NP_001336793.1:p.Arg710His
  • NP_001336794.1:p.Arg656His
  • NP_001336795.1:p.Arg656His
  • NP_001336796.1:p.Arg532His
  • NP_001336797.1:p.Arg484His
  • NP_001336798.1:p.Arg478His
  • NP_003551.2:p.Arg710His
  • LRG_1015t1:c.2129G>A
  • LRG_1015:g.106219G>A
  • LRG_1015p1:p.Arg710His
  • NC_000022.10:g.38509567C>T
  • NM_001199562.1:c.1967G>A
  • NM_003560.2:c.2129G>A
Protein change:
R478H
Links:
dbSNP: rs147455037
NCBI 1000 Genomes Browser:
rs147455037
Molecular consequence:
  • NM_001004426.3:c.1967G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199562.3:c.1967G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349864.2:c.2129G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349865.2:c.1967G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349866.2:c.1967G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349867.2:c.1595G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349868.2:c.1451G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349869.2:c.1433G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003560.4:c.2129G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Infantile neuroaxonal dystrophy (NBIA2A)
Synonyms:
NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 2A; Seitelberger disease
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
SCV000943938Invitaecriteria provided, single submitter
Uncertain significance
(Dec 20, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000943938.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine with histidine at codon 710 of the PLA2G6 protein (p.Arg710His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs147455037, ExAC 0.01%). This variant has been observed in an individual affected with intellectual disability, epilepsy, cortical atrophy, and cerebellar hypoplasia (PMID: 26539891). This variant is also known as NM_001199562: c.G1967A; p.R656H in the literature. ClinVar contains an entry for this variant (Variation ID: 402191). 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: "Probably 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.

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

Last Updated: Oct 24, 2021

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