chr1-19978510-G-A

Position:

chr1-19978510-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001395463.1(PLA2G2A):c.55C>T(p.His19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,613,646 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0065 ( 20 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 107 hom. )

Consequence

PLA2G2A
NM_001395463.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.463

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006665617).

BP6

Variant 1-19978510-G-A is Benign according to our data. Variant chr1-19978510-G-A is described in ClinVar as [Benign]. Clinvar id is 712953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00645 (983/152302) while in subpopulation EAS AF= 0.0332 (172/5180). AF 95% confidence interval is 0.0292. There are 20 homozygotes in gnomad4. There are 622 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1 linkuse as main transcript	c.55C>T	p.His19Tyr	missense_variant	3/5	ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3 linkuse as main transcript	c.55C>T	p.His19Tyr	missense_variant	3/5	1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes

AF:

0.00643

AC:

979

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0475

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0106

AC:

2657

AN:

251110

Hom.:

AF XY:

0.00969

AC XY:

1315

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.0288

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.00312

Gnomad OTH exome

AF:

0.00978

GnomAD4 exome

AF:

0.00434

AC:

6343

AN:

1461344

Hom.:

107

Cov.:

AF XY:

0.00409

AC XY:

2976

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0175

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.000927

Gnomad4 FIN exome

AF:

0.0471

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.00493

GnomAD4 genome

AF:

0.00645

AC:

983

AN:

152302

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

622

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0332

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0475

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00372

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00937

AC:

1138

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

PLA2G2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 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

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.5

DANN

Benign

0.94

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.22

T;.

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.016

Sift

Benign

0.11

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0040

B;B

Vest4

0.18

MPC

0.60

ClinPred

0.0022

GERP RS

2.9

Varity_R

0.094

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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