6-46704644-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005084.4(PLA2G7):c.1242G>T(p.Glu414Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0006 in 1,577,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Publications

7 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01131922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4 link	c.1242G>T	p.Glu414Asp	missense_variant	Exon 12 of 12	ENST00000274793.12	NP_005075.3	Q13093
PLA2G7	NM_001168357.2 link	c.1242G>T	p.Glu414Asp	missense_variant	Exon 12 of 12		NP_001161829.1	Q13093
PLA2G7	XM_005249408.5 link	c.1242G>T	p.Glu414Asp	missense_variant	Exon 12 of 12		XP_005249465.1	Q13093
PLA2G7	XM_047419359.1 link	c.1107G>T	p.Glu369Asp	missense_variant	Exon 11 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12 link	c.1242G>T	p.Glu414Asp	missense_variant	Exon 12 of 12	1	NM_005084.4	ENSP00000274793.7		Q13093
PLA2G7	ENST00000537365.1 link	c.1242G>T	p.Glu414Asp	missense_variant	Exon 12 of 12	1		ENSP00000445666.1		Q13093

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000526

AC:

132

AN:

250988

AF XY:

0.000494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000687

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000599

AC:

854

AN:

1425692

Hom.:

Cov.:

AF XY:

0.000568

AC XY:

404

AN XY:

711720

show subpopulations

African (AFR)

AF:

0.0000912

AC:

AN:

32878

American (AMR)

AF:

0.00135

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25922

East Asian (EAS)

AF:

0.00

AC:

AN:

39466

South Asian (SAS)

AF:

0.00

AC:

AN:

85598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.000698

AC:

753

AN:

1078960

Other (OTH)

AF:

0.000625

AC:

AN:

59190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000605

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41514

American (AMR)

AF:

0.00203

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000670

Hom.:

Bravo

AF:

0.000597

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000437

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000830

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: PLA2G7 c.1242G>T (p.Glu414Asp) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00053 in 250988 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in PLA2G7 causing Platelet-Activating Factor Acetylhydrolase Deficiency, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1242G>T in individuals affected with Platelet-Activating Factor Acetylhydrolase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.5

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.052

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.18

.;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.39

N;N

PhyloP100

-1.1

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.090

Sift

Benign

0.47

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;B

Vest4

0.093

MutPred

0.54

Loss of disorder (P = 0.277);Loss of disorder (P = 0.277);

MVP

0.24

MPC

0.0051

ClinPred

0.0091

GERP RS

-5.9

Varity_R

0.16

gMVP

0.33

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

6-46704644-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over