chr6-46709361-C-A

Position:

chr6-46709361-C-A

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.79

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 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 linkuse as main transcript	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 linkuse as main transcript	c.835G>T	p.Val279Phe	missense_variant	9/12	1	NM_005084.4	P1
PLA2G7	ENST00000537365.1 linkuse as main transcript	c.835G>T	p.Val279Phe	missense_variant	9/12	1		P1

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

GnomAD3 exomes

AF:

0.00455

AC:

1141

AN:

251010

Hom.:

AF XY:

0.00425

AC XY:

576

AN XY:

135680

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 SAS exome

AF:

0.000719

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

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00223

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.000860

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.0000976

Gnomad4 OTH exome

AF:

0.00233

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152210

Hom.:

Cov.:

AF XY:

0.00308

AC XY:

229

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00249

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

Significance: Benign

Submissions summary: Pathogenic:1Benign:2Other:1

Revision: criteria provided, single submitter

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, no assertion criteria provided

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;D

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

.;D

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

0.000029

P;P

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.5

N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

1.0

D;D

Vest4

0.87

MVP

0.51

MPC

0.020

ClinPred

0.099

GERP RS

5.1

Varity_R

0.97

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over