NM_005084.4(PLA2G7):c.663+1G>A AND Platelet-activating factor acetylhydrolase deficiency

Germline classification:: Pathogenic; risk factor (2 submissions)
Last evaluated:: Jan 6, 2020
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000578126.3

Allele description [Variation Report for NM_005084.4(PLA2G7):c.663+1G>A]

NM_005084.4(PLA2G7):c.663+1G>A

Gene:

PLA2G7:phospholipase A2 group VII [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.3

Genomic location:

Preferred name:

NM_005084.4(PLA2G7):c.663+1G>A

HGVS:

NC_000006.12:g.46711495C>T
NG_016204.1:g.29199G>A
NM_001168357.2:c.663+1G>A
NM_005084.4:c.663+1G>AMANE SELECT
NC_000006.11:g.46679232C>T
NM_001168357.1:c.663+1G>A
NM_005084.3:c.663+1G>A

Nucleotide change:

NT663, G-A, +1

Links:

OMIM: 601690.0004; dbSNP: rs201899866

NCBI 1000 Genomes Browser:

rs201899866

Molecular consequence:

NM_001168357.2:c.663+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_005084.4:c.663+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Platelet-activating factor acetylhydrolase deficiency (PAFAD)
Identifiers:: MONDO: MONDO:0013663; MedGen: C3280315; OMIM: 614278; Human Phenotype Ontology: HP:0040175

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000679983	OMIM	no assertion criteria provided	Pathogenic (Jan 24, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001142359	Reproductive Health Research and Development, BGI Genomics	no assertion criteria provided	risk factor (Jan 6, 2020)	germline	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000679983

OMIM

no assertion criteria provided

Pathogenic
(Jan 24, 2018)

germline

literature only

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

SCV001142359

Reproductive Health Research and Development, BGI Genomics

no assertion criteria provided

risk factor
(Jan 6, 2020)

germline

curation

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA, Won HH, Karczewski KJ, O'Donnell-Luria AH, Samocha KE, Weisburd B, Gupta N, Zaidi M, Samuel M, Imran A, Abbas S, Majeed F, Ishaq M, Akhtar S, Trindade K, Mucksavage M, Qamar N, et al.

Nature. 2017 Apr 12;544(7649):235-239. doi: 10.1038/nature22034.

PubMed [citation]

PMID:: 28406212
PMCID:: PMC5600291

Details of each submission

From OMIM, SCV000679983.1

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

Description

Among the 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), Saleheen et al. (2017) identified participants who were naturally deficient in the Lp-PLA2 enzyme (PAFAD; 614278). Two participants were homozygous for a splice-site mutation, c.663+1G-A (c.663+1G-A, ENST00000274793.7), and 106 were heterozygous for the same mutation. Saleheen et al. (2017) observed a dose-dependent response relationship between genotype and enzymatic activity. Compared with noncarriers, c.663+1G-A homozygotes had markedly lower Lp-PLA2 enzymatic activity (-245 nmol/ml/min, p = 2 x 10(-7)), whereas the 106 heterozygotes had an intermediate effect (-120 nmol/ml/min, p = 2 x 10(-77)). Homozygosity for predicted loss-of-function mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Reproductive Health Research and Development, BGI Genomics, SCV001142359.1

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

Description

NG_016204.1(NM_001168357.1):c.663+1G>A in the PLA2G7 gene has an allele frequency of 0.008 in South Asian subpopulation in the gnomAD database, including three homozygotes. The c.663+1G>A variant destroys the canonical splice donor site in intron 13. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product if the message is used for protein translation. However, activity of soluble lipoprotein-associated phospholipase A2 (encoded by PLA2G7) has been correlated with risk for coronary heart disease (PMID: 28406212). Taken together, we interprete this variant as risk factor variant.

#	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: Dec 24, 2023

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