Variant chr1-19922313-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014589.3(PLA2G2E):c.271C>G(p.Arg91Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

PLA2G2E
NM_014589.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.13

Variant links:

Genes affected

PLA2G2E (HGNC:13414): (phospholipase A2 group IIE) Enables calcium ion binding activity and calcium-dependent phospholipase A2 activity. Predicted to be involved in phospholipid metabolic process. Predicted to act upstream of or within low-density lipoprotein particle remodeling. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PLA2G2E links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025535315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2E	NM_014589.3 linkuse as main transcript	c.271C>G	p.Arg91Gly	missense_variant	3/4	ENST00000375116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2E	ENST00000375116.3 linkuse as main transcript	c.271C>G	p.Arg91Gly	missense_variant	3/4	1	NM_014589.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 16, 2021

The c.271C>G (p.R91G) alteration is located in exon 3 (coding exon 3) of the PLA2G2E gene. This alteration results from a C to G substitution at nucleotide position 271, causing the arginine (R) at amino acid position 91 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.045

DANN

Benign

0.20

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.12

M_CAP

Benign

0.0042

MetaRNN

Benign

0.026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

4.6

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.52

Gain of catalytic residue at G92 (P = 0.0761);

MVP

0.21

MPC

0.29

ClinPred

0.099

GERP RS

-9.6

Varity_R

0.24

gMVP

0.28

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