1-19978469-C-G

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.96G>C(p.Thr32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 1,613,622 control chromosomes in the GnomAD database, including 8,138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (646 hom., cov: 32)
  • Exomes 𝑓: 0.094 (7492 hom.)
• Consequence: PLA2G2A NM_001395463.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

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=-0.81).
• BP6: Variant 1-19978469-C-G is Benign according to our data. Variant chr1-19978469-C-G is described in ClinVar as [Benign]. Clinvar id is 3059119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1	c.96G>C	p.Thr32=	synonymous_variant	3/5	ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.96G>C	p.Thr32=	synonymous_variant	3/5	1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11828 AN: 152076 Hom.: 650 Cov.: 32

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0690

GnomAD3 exomes AF: 0.109 AC: 27504 AN: 251184 Hom.: 1811 AF XY: 0.109 AC XY: 14777 AN XY: 135766

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.225

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0966

Gnomad NFE exome AF: 0.0881

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0943 AC: 137803 AN: 1461428 Hom.: 7492 Cov.: 36 AF XY: 0.0947 AC XY: 68840 AN XY: 727022

Gnomad4 AFR exome AF: 0.0140

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.0863

Gnomad4 OTH exome AF: 0.0954

GnomAD4 genome AF: 0.0776 AC: 11817 AN: 152194 Hom.: 646 Cov.: 32 AF XY: 0.0818 AC XY: 6083 AN XY: 74382

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0973

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0669

Alfa AF: 0.0827 Hom.: 153

Bravo AF: 0.0788

Asia WGS AF: 0.149 AC: 518 AN: 3476

EpiCase AF: 0.0839

EpiControl AF: 0.0887

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

Nov 19, 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	-0.81
Cadd	Benign	0.83
Dann	Benign	0.40

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: rs2236771; hg19: chr1-20304962; COSMIC: COSV64287129;