Genetic Variant PLA2G7:p.Val279Phe (chr6-46709361-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter P:1B:2O:1

Conservation

PhyloP100: 2.79

Publications

117 publications found

Variant links:

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]

PLA2G7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022307456).

BP6

Variant 6-46709361-C-A is Benign according to our data. Variant chr6-46709361-C-A is described in ClinVar as Benign. ClinVar VariationId is 7914.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005084.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.835G>T	p.Val279Phe	missense	Exon 9 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.835G>T	p.Val279Phe	missense	Exon 9 of 12	NP_001161829.1	Q13093

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.835G>T	p.Val279Phe	missense	Exon 9 of 12	ENSP00000274793.7	Q13093
PLA2G7	ENST00000537365.1	TSL:1	c.835G>T	p.Val279Phe	missense	Exon 9 of 12	ENSP00000445666.1	Q13093
PLA2G7	ENST00000878321.1		c.835G>T	p.Val279Phe	missense	Exon 9 of 12	ENSP00000548380.1

Frequencies

GnomAD3 genomes

AF:

0.00268

AC:

408

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0726

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00455

AC:

1141

AN:

251010

AF XY:

0.00425

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.0575

Gnomad FIN exome

AF:

0.0000927

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00362

AC:

5270

AN:

1455538

Hom.:

378

Cov.:

AF XY:

0.00354

AC XY:

2562

AN XY:

724626

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33328

American (AMR)

AF:

0.0000671

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00223

AC:

AN:

26040

East Asian (EAS)

AF:

0.124

AC:

4877

AN:

39486

South Asian (SAS)

AF:

0.000860

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.0000563

AC:

AN:

53256

Middle Eastern (MID)

AF:

0.000870

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000976

AC:

108

AN:

1106752

Other (OTH)

AF:

0.00233

AC:

140

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

225

450

676

901

1126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152210

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41538

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.0726

AC:

376

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68010

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.00232

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00484

AC:

587

Asia WGS

AF:

0.0300

AC:

105

AN:

3468

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

PLA2G7-related disorder (1)

Platelet-activating factor acetylhydrolase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

2.9

PhyloP100

2.8

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.38

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.87

MVP

0.51

MPC

0.020

ClinPred

0.099

GERP RS

5.1

Varity_R

0.97

gMVP

0.89

Mutation Taster

=50/50

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over