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NM_003560.4(PLA2G6):c.1798C>T (p.Arg600Trp) AND Neurodegeneration with brain iron accumulation

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 5, 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:
RCV002266002.1

Allele description [Variation Report for NM_003560.4(PLA2G6):c.1798C>T (p.Arg600Trp)]

NM_003560.4(PLA2G6):c.1798C>T (p.Arg600Trp)

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.1798C>T (p.Arg600Trp)
Other names:
NM_003560.4(PLA2G6):c.1798C>T; p.Arg600Trp
HGVS:
  • NC_000022.11:g.38116156G>A
  • NG_007094.3:g.103623C>T
  • NM_001004426.3:c.1636C>T
  • NM_001199562.3:c.1636C>T
  • NM_001349864.2:c.1798C>T
  • NM_001349865.2:c.1636C>T
  • NM_001349866.2:c.1636C>T
  • NM_001349867.2:c.1264C>T
  • NM_001349868.2:c.1120C>T
  • NM_001349869.2:c.1102C>T
  • NM_003560.4:c.1798C>TMANE SELECT
  • NP_001004426.1:p.Arg546Trp
  • NP_001186491.1:p.Arg546Trp
  • NP_001336793.1:p.Arg600Trp
  • NP_001336794.1:p.Arg546Trp
  • NP_001336795.1:p.Arg546Trp
  • NP_001336796.1:p.Arg422Trp
  • NP_001336797.1:p.Arg374Trp
  • NP_001336798.1:p.Arg368Trp
  • NP_003551.2:p.Arg600Trp
  • LRG_1015t1:c.1798C>T
  • LRG_1015:g.103623C>T
  • LRG_1015p1:p.Arg600Trp
  • NC_000022.10:g.38512163G>A
  • NC_000022.10:g.38512163G>A
  • NG_007094.2:g.94535C>T
  • NM_003560.2:c.1798C>T
Protein change:
R368W
Links:
dbSNP: rs368008077
NCBI 1000 Genomes Browser:
rs368008077
Molecular consequence:
  • NM_001004426.3:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001199562.3:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349864.2:c.1798C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349865.2:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349866.2:c.1636C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349867.2:c.1264C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349868.2:c.1120C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001349869.2:c.1102C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003560.4:c.1798C>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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002548272Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(May 5, 2022) 		germlineclinical testing

PubMed (6)
[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

Genetic Analysis of PLA2G6 in 22 Indian Families with Infantile Neuroaxonal Dystrophy, Atypical Late-Onset Neuroaxonal Dystrophy and Dystonia Parkinsonism Complex.

Kapoor S, Shah MH, Singh N, Rather MI, Bhat V, Gopinath S, Bindu PS, Taly AB, Sinha S, Nagappa M, Bharath RD, Mahadevan A, Narayanappa G, Chickabasaviah YT, Kumar A.

PLoS One. 2016;11(5):e0155605. doi: 10.1371/journal.pone.0155605.

PubMed [citation]
PMID:
27196560
PMCID:
PMC4873246

The natural history of infantile neuroaxonal dystrophy.

Altuame FD, Foskett G, Atwal PS, Endemann S, Midei M, Milner P, Salih MA, Hamad M, Al-Muhaizea M, Hashem M, Alkuraya FS.

Orphanet J Rare Dis. 2020 May 1;15(1):109. doi: 10.1186/s13023-020-01355-2.

PubMed [citation]
PMID:
32357911
PMCID:
PMC7193406
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548272.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: PLA2G6 c.1798C>T (p.Arg600Trp) 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 1.6e-05 in 251070 control chromosomes (gnomAD). c.1798C>T has been reported in the literature in multiple compound heterozygous individuals affected with PLA2G6-associated neurodegeneration (Illingworth_2014, Jain_2019, Altuame_2020). Additionally, this variant was found in three affected siblings and co-segregated with disease (Toth-Bencsik_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. Another missense variant (p.Arg600Gln) at the same residue was found in patients with Infantile neuroaxonal dystrophy (Kapoor_2016, HGMD database) and has been classified as likely pathogenic/pathogenic in ClinVar, suggesting that it is a clinically significant residue. One ClinVar submitter (evaluation after 2014) cites the variant as likely 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: Sep 29, 2024