U.S. flag

An official website of the United States government

NM_003560.4(PLA2G6):c.991G>A (p.Asp331Asn) AND PLA2G6-associated neurodegeneration

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 24, 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:
RCV001146572.7

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:
PLA2G6-associated neurodegeneration (PLAN)
Synonyms:
phospholipase A2-associated neurodegeneration
Identifiers:
MONDO: MONDO:0017998; MedGen: CN204472; Orphanet: 329303

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001307322Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)		Uncertain significance
(Sep 5, 2017) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV003761013Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 24, 2023) 		germlinecuration

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

Help

Summary from all submissions

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

Citations

PubMed

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

PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort.

Shi CH, Tang BS, Wang L, Lv ZY, Wang J, Luo LZ, Shen L, Jiang H, Yan XX, Pan Q, Xia K, Guo JF.

Neurology. 2011 Jul 5;77(1):75-81. doi: 10.1212/WNL.0b013e318221acd3. Epub 2011 Jun 22.

PubMed [citation]
PMID:
21700586
See all PubMed Citations (5)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001307322.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761013.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The p.Asp331Asn variant in PLA2G6 has not been previously reported in the literature in individuals with PLA2G6-associated neurodegeneration but has been identified in 0.009% (7/81550) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs199935023). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 522939) and has been interpreted as pathogenic by Genomic Research Center (Shahid Beheshti University of Medical Sciences) and as a variant of uncertain significance by Invitae, CeGaT Center for Human Genetics Tuebingen, and Illumina Laboratory Services (Illumina). Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. One additional pathogenic variant, resulting in a different amino acid change at the same position, p.Asp331Tyr, has been reported in association with disease in the literature and ClinVar, supporting that a change at this position may not be tolerated (PMID: 29454663, 31196701, 22213678/Variation ID: 30371). In summary, the clinical significance of the p.Asp331Asn variant is uncertain. ACMG/AMP Criteria applied: BP4, PM2_supporting, PM5 (Richards 2015).

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

Last Updated: Oct 8, 2024