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NM_003560.4(PLA2G6):c.1894C>T (p.Arg632Trp) AND Neurodegeneration with brain iron accumulation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 10, 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:
RCV001582469.3

Allele description [Variation Report for NM_003560.4(PLA2G6):c.1894C>T (p.Arg632Trp)]

NM_003560.4(PLA2G6):c.1894C>T (p.Arg632Trp)

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.1894C>T (p.Arg632Trp)
Other names:
NM_003560.4(PLA2G6):c.1894C>T
HGVS:
  • NC_000022.11:g.38115667G>A
  • NG_007094.3:g.104112C>T
  • NG_033059.2:g.3C>T
  • NM_001004426.3:c.1732C>T
  • NM_001199562.3:c.1732C>T
  • NM_001349864.2:c.1894C>T
  • NM_001349865.2:c.1732C>T
  • NM_001349866.2:c.1732C>T
  • NM_001349867.2:c.1360C>T
  • NM_001349868.2:c.1216C>T
  • NM_001349869.2:c.1198C>T
  • NM_003560.4:c.1894C>TMANE SELECT
  • NP_001004426.1:p.Arg578Trp
  • NP_001186491.1:p.Arg578Trp
  • NP_001336793.1:p.Arg632Trp
  • NP_001336794.1:p.Arg578Trp
  • NP_001336795.1:p.Arg578Trp
  • NP_001336796.1:p.Arg454Trp
  • NP_001336797.1:p.Arg406Trp
  • NP_001336798.1:p.Arg400Trp
  • NP_003551.2:p.Arg632Trp
  • LRG_1015t1:c.1894C>T
  • LRG_1015:g.104112C>T
  • LRG_1015p1:p.Arg632Trp
  • NC_000022.10:g.38511674G>A
  • NC_000022.10:g.38511674G>A
  • NG_007094.2:g.95024C>T
  • NM_003560.2:c.1894C>T
  • O60733:p.Arg632Trp
Protein change:
R400W; ARG632TRP
Links:
UniProtKB: O60733#VAR_029373; OMIM: 603604.0005; dbSNP: rs121908683
NCBI 1000 Genomes Browser:
rs121908683
Molecular consequence:
  • NM_001004426.3:c.1732C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199562.3:c.1732C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349864.2:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349865.2:c.1732C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349866.2:c.1732C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349867.2:c.1360C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349868.2:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349869.2:c.1198C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003560.4:c.1894C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neurodegeneration with brain iron accumulation (NBIA)
Identifiers:
MONDO: MONDO:0018307; MedGen: C2931845; OMIM: PS234200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001821509Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Aug 10, 2021) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

PARK14 PLA2G6 mutants are defective in preventing rotenone-induced mitochondrial dysfunction, ROS generation and activation of mitochondrial apoptotic pathway.

Chiu CC, Yeh TH, Lu CS, Huang YC, Cheng YC, Huang YZ, Weng YH, Liu YC, Lai SC, Chen YL, Chen YJ, Chen CL, Chen HY, Lin YW, Wang HL.

Oncotarget. 2017 Oct 3;8(45):79046-79060. doi: 10.18632/oncotarget.20893.

PubMed [citation]
PMID:
29108286
PMCID:
PMC5668019

Catalytic function of PLA2G6 is impaired by mutations associated with infantile neuroaxonal dystrophy but not dystonia-parkinsonism.

Engel LA, Jing Z, O'Brien DE, Sun M, Kotzbauer PT.

PLoS One. 2010 Sep 23;5(9):e12897. doi: 10.1371/journal.pone.0012897.

PubMed [citation]
PMID:
20886109
PMCID:
PMC2944820
See all PubMed Citations (11)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001821509.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

Variant summary: PLA2G6 c.1894C>T (p.Arg632Trp) results in a non-conservative amino acid change located in the Patatin-like phospholipase domain (IPR002641) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9e-06 in 223138 control chromosomes. c.1894C>T has been reported in the literature in multiple individuals affected with Neurodegeneration With Brain Iron Accumulation (example Sina_2009, Morgan_2006) and subsequently cited by others (example, Kapoor_2016, pei Guo_2018, Giri_2016, Shen_2019, Tsai Chu_2020, and Yup Lee_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 20, 2024