Variant 1-19975708-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395463.1(PLA2G2A):c.428G>A(p.Arg143His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,613,616 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 42 hom. )

Consequence

PLA2G2A
NM_001395463.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

Variant links:

Genes affected

PLA2G2A (HGNC:9031): (phospholipase A2 group IIA) The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

PLA2G2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008064479).

BP6

Variant 1-19975708-C-T is Benign according to our data. Variant chr1-19975708-C-T is described in ClinVar as [Benign]. Clinvar id is 3038442.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1 linkuse as main transcript	c.428G>A	p.Arg143His	missense_variant	5/5	ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3 linkuse as main transcript	c.428G>A	p.Arg143His	missense_variant	5/5	1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

655

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00726

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00465

AC:

1169

AN:

251482

Hom.:

AF XY:

0.00489

AC XY:

665

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00428

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00735

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00684

AC:

9996

AN:

1461430

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

4854

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00288

Gnomad4 ASJ exome

AF:

0.00130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00451

Gnomad4 FIN exome

AF:

0.00139

Gnomad4 NFE exome

AF:

0.00804

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00430

AC:

655

AN:

152186

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

278

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00726

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00624

Hom.:

Bravo

AF:

0.00434

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.00477

AC:

579

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PLA2G2A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

Cadd

Benign

8.1

Dann

Benign

0.92

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.52

T;T;.

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0081

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

Polyphen

0.78

.;P;P

Vest4

0.10, 0.10

MVP

0.25

MPC

0.73

ClinPred

0.012

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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