NM_003560.4(PLA2G6):c.986G>A (p.Arg329His) AND PLA2G6-associated neurodegeneration

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 2023
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:: RCV002514840.3

Allele description [Variation Report for NM_003560.4(PLA2G6):c.986G>A (p.Arg329His)]

NM_003560.4(PLA2G6):c.986G>A (p.Arg329His)

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.986G>A (p.Arg329His)

Other names:

NM_003560.4(PLA2G6):c.986G>A; p.Arg329His

HGVS:

NC_000022.11:g.38132922C>T
NG_007094.3:g.86857G>A
NM_001004426.3:c.986G>A
NM_001199562.3:c.986G>A
NM_001349864.2:c.986G>A
NM_001349865.2:c.986G>A
NM_001349866.2:c.986G>A
NM_001349867.2:c.452G>A
NM_001349868.2:c.308G>A
NM_001349869.2:c.452G>A
NM_003560.4:c.986G>AMANE SELECT
NP_001004426.1:p.Arg329His
NP_001186491.1:p.Arg329His
NP_001336793.1:p.Arg329His
NP_001336794.1:p.Arg329His
NP_001336795.1:p.Arg329His
NP_001336796.1:p.Arg151His
NP_001336797.1:p.Arg103His
NP_001336798.1:p.Arg151His
NP_003551.2:p.Arg329His
LRG_1015t1:c.986G>A
LRG_1015:g.86857G>A
LRG_1015p1:p.Arg329His
NC_000022.10:g.38528929C>T
NG_007094.2:g.77769G>A
NM_003560.2:c.986G>A

Protein change:

R103H

Links:

dbSNP: rs587784363

NCBI 1000 Genomes Browser:

rs587784363

Molecular consequence:

NM_001004426.3:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.986G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349867.2:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349868.2:c.308G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349869.2:c.452G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.986G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003761014	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 24, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003761014

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 24, 2023)

germline

curation

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	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761014.1

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

Description

The p.Arg329His variant in PLA2G6 has been reported in 3 individuals. in the compound heterozygous state, with PLA2G6-associated neurodegeneration (PMID: 34256386, 27516098, 33098801) and has been identified in 0.006% (5/82514) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs587784363). 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. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg329His variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting (Richards 2015).

#	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: Oct 20, 2024

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