NM_003560.4(PLA2G6):c.386T>C (p.Leu129Pro) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 1, 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:: RCV000623680.6

Allele description [Variation Report for NM_003560.4(PLA2G6):c.386T>C (p.Leu129Pro)]

NM_003560.4(PLA2G6):c.386T>C (p.Leu129Pro)

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.386T>C (p.Leu129Pro)

Other names:

NM_003560.4(PLA2G6):c.386T>C; p.Leu129Pro; p.L129P

HGVS:

NC_000022.11:g.38145477A>G
NG_007094.3:g.74302T>C
NM_001004426.3:c.386T>C
NM_001199562.3:c.386T>C
NM_001349864.2:c.386T>C
NM_001349865.2:c.386T>C
NM_001349866.2:c.386T>C
NM_001349867.2:c.-149T>C
NM_001349868.2:c.-105T>C
NM_001349869.2:c.-149T>C
NM_003560.3:c.386T>C
NM_003560.4:c.386T>CMANE SELECT
NP_001004426.1:p.Leu129Pro
NP_001186491.1:p.Leu129Pro
NP_001336793.1:p.Leu129Pro
NP_001336794.1:p.Leu129Pro
NP_001336795.1:p.Leu129Pro
NP_003551.2:p.Leu129Pro
LRG_1015t1:c.386T>C
LRG_1015:g.74302T>C
LRG_1015p1:p.Leu129Pro
NC_000022.10:g.38541484A>G
NG_007094.2:g.65214T>C
NM_003560.2:c.386T>C
NM_003560.4:c.386T>C

Protein change:

L129P

Links:

dbSNP: rs374746113

NCBI 1000 Genomes Browser:

rs374746113

Molecular consequence:

NM_001349867.2:c.-149T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001349868.2:c.-105T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001349869.2:c.-149T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001004426.3:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001199562.3:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349864.2:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349865.2:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001349866.2:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003560.4:c.386T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000742160	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Sep 1, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29395073, 29859652 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000742160

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Sep 1, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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	clinical testing

Citations

PubMed

Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation.

Drecourt A, Babdor J, Dussiot M, Petit F, Goudin N, Garfa-Traoré M, Habarou F, Bole-Feysot C, Nitschké P, Ottolenghi C, Metodiev MD, Serre V, Desguerre I, Boddaert N, Hermine O, Munnich A, Rötig A.

Am J Hum Genet. 2018 Feb 1;102(2):266-277. doi: 10.1016/j.ajhg.2018.01.003.

PubMed [citation]

PMID:: 29395073
PMCID:: PMC5985451

PLA2G6-associated neurodegeneration: Lessons from neurophysiological findings.

Gitiaux C, Kaminska A, Boddaert N, Barcia G, Guéden S, The Tich SN, De Lonlay P, Quijano-Roy S, Hully M, Péréon Y, Desguerre I.

Eur J Paediatr Neurol. 2018 Sep;22(5):854-861. doi: 10.1016/j.ejpn.2018.05.005. Epub 2018 May 22.

PubMed [citation]

PMID:: 29859652

Details of each submission

From Ambry Genetics, SCV000742160.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The c.386T>C (p.L129P) alteration is located in exon 3 (coding exon 2) of the PLA2G6 gene. This alteration results from a T to C substitution at nucleotide position 386, causing the leucine (L) at amino acid position 129 to be replaced by a proline (P). Based on data from gnomAD, the C allele has an overall frequency of 0.01% (14/278142) total alleles studied. The highest observed frequency was 0.06% (14/24504) of African alleles. The p.L129P alteration has detected in the homozygous state and in trans with other PLA2G6 alterations in patients with features consistent with neurodegeneration with brain iron accumulation (Drecourt, 2018; Gitiaux, 2018; Ambry internal data). This amino acid position is well conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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: Sep 16, 2024

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