rs2307246

Positions:

• chr1-19978364-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395463.1(PLA2G2A):​c.185+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,608,878 control chromosomes in the GnomAD database, including 36,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2800 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33979 hom.)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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.185+16C>T		intron_variant		ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.185+16C>T		intron_variant		1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26736 AN: 152064 Hom.: 2795 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.175 AC: 43559 AN: 248664 Hom.: 4599 AF XY: 0.177 AC XY: 23868 AN XY: 134518

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.0886

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.0296

Gnomad SAS exome AF: 0.121

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.208 AC: 303597 AN: 1456696 Hom.: 33979 Cov.: 34 AF XY: 0.207 AC XY: 149821 AN XY: 724520

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0944

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.0185

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.176 AC: 26757 AN: 152182 Hom.: 2800 Cov.: 32 AF XY: 0.173 AC XY: 12900 AN XY: 74410

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.175

Alfa AF: 0.209 Hom.: 3578

Bravo AF: 0.161

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.38

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: rs2307246; hg19: chr1-20304857; COSMIC: COSV64286990;