Variant chr1-19978381-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001395463.1(PLA2G2A):c.184C>T(p.Arg62Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R62R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PLA2G2A
NM_001395463.1 missense, splice_region

Scores

Splicing: ADA: 0.0001745

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.99

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1 linkuse as main transcript	c.184C>T	p.Arg62Cys	missense_variant, splice_region_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.184C>T	p.Arg62Cys	missense_variant, splice_region_variant	3/5	1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250118

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1459794

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 19, 2023

The c.184C>T (p.R62C) alteration is located in exon 4 (coding exon 2) of the PLA2G2A gene. This alteration results from a C to T substitution at nucleotide position 184, causing the arginine (R) at amino acid position 62 to be replaced by a cysteine (C). 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.40

CADD

Benign

0.49

DANN

Benign

0.96

DEOGEN2

Benign

0.42

.;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0037

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.8

.;H;H

MutationTaster

Benign

0.88

N;N

PrimateAI

Benign

0.19

PROVEAN

Pathogenic

-5.1

.;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.014

.;D;D

Sift4G

Uncertain

0.014

.;D;D

Polyphen

0.76

.;P;P

Vest4

0.48, 0.48

MutPred

0.76

.;Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.37

MPC

1.7

ClinPred

0.47

GERP RS

-10

Varity_R

0.18

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.27

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