rs4744

chr1-19978433-G-Achr1-19978433-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001395463.1(PLA2G2A):c.132C>T(p.Tyr44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,611,986 control chromosomes in the GnomAD database, including 36,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2794 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33985 hom.)
• Consequence: PLA2G2A NM_001395463.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.456

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-19978433-G-A is Benign according to our data. Variant chr1-19978433-G-A is described in ClinVar as [Benign]. Clinvar id is 3056896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.456 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1	c.132C>T	p.Tyr44=	synonymous_variant	3/5	ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.132C>T	p.Tyr44=	synonymous_variant	3/5	1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26744 AN: 152026 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0240

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.176 AC: 43563 AN: 246998 Hom.: 4668 AF XY: 0.178 AC XY: 23964 AN XY: 134344

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0900

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0300

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.208 AC: 304039 AN: 1459840 Hom.: 33985 Cov.: 36 AF XY: 0.207 AC XY: 150044 AN XY: 726290

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0958

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.176 AC: 26767 AN: 152146 Hom.: 2794 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74378

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.177

Alfa AF: 0.198 Hom.: 4015

Bravo AF: 0.161

Asia WGS AF: 0.0770 AC: 267 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLA2G2A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 25, 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
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.8
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs4744; hg19: chr1-20304926; COSMIC: COSV64286997;