rs76863441
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_005084.4(PLA2G7):c.835G>T(p.Val279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,607,748 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0027 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 378 hom. )
Consequence
PLA2G7
NM_005084.4 missense
NM_005084.4 missense
Scores
2
10
5
Clinical Significance
Conservation
PhyloP100: 2.79
Genes affected
PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.022307456).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLA2G7 | NM_005084.4 | c.835G>T | p.Val279Phe | missense_variant | 9/12 | ENST00000274793.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLA2G7 | ENST00000274793.12 | c.835G>T | p.Val279Phe | missense_variant | 9/12 | 1 | NM_005084.4 | P1 | |
PLA2G7 | ENST00000537365.1 | c.835G>T | p.Val279Phe | missense_variant | 9/12 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00268 AC: 408AN: 152092Hom.: 21 Cov.: 32
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GnomAD3 exomes AF: 0.00455 AC: 1141AN: 251010Hom.: 40 AF XY: 0.00425 AC XY: 576AN XY: 135680
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GnomAD4 exome AF: 0.00362 AC: 5270AN: 1455538Hom.: 378 Cov.: 27 AF XY: 0.00354 AC XY: 2562AN XY: 724626
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GnomAD4 genome ? AF: 0.00267 AC: 406AN: 152210Hom.: 21 Cov.: 32 AF XY: 0.00308 AC XY: 229AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Platelet-activating factor acetylhydrolase deficiency Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2006 | - - |
risk factor, no assertion criteria provided | curation | Reproductive Health Research and Development, BGI Genomics | Jan 06, 2020 | NM_005084.3:c.835G>T in the PLA2G7 gene has an allele frequency of 0.056 in East Asian subpopulation in the gnomAD database, including 41 homozygous occurrences. This variant has been reported as a genetic risk factor for stroke, asthma and cardiovascular disease (PMID: 9412624, 10194471, 16787988). Taken together, we interprete this variant as risk factor variant. - |
PLA2G7-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 18, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2020 | This variant is associated with the following publications: (PMID: 21834908, 19373214, 20080080, 20185515, 19034521, 9472966, 21606947, 21490708, 20926117, 16086290, 8675689, 11916011, 10194471, 9759612, 9412624, 16787988, 26595893, 26791069, 31589614, 11248283) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Uncertain
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at