rs2236772

Positions:

• chr1-19978292-C-T

Variant summary

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

The NM_001395463.1(PLA2G2A):​c.185+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,498,284 control chromosomes in the GnomAD database, including 1,426 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 0.032 (130 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1296 hom.)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G2A	NM_001395463.1	c.185+88G>A		intron_variant		ENST00000482011.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.185+88G>A		intron_variant		1	NM_001395463.1	P1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4935 AN: 152128 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.00753

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0353 AC: 47496 AN: 1346038 Hom.: 1296 Cov.: 20 AF XY: 0.0360 AC XY: 24214 AN XY: 673118

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0828

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0664

Gnomad4 FIN exome AF: 0.0286

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.0390

GnomAD4 genome AF: 0.0324 AC: 4931 AN: 152246 Hom.: 130 Cov.: 33 AF XY: 0.0350 AC XY: 2609 AN XY: 74444

Gnomad4 AFR AF: 0.00748

Gnomad4 AMR AF: 0.0799

Gnomad4 ASJ AF: 0.0837

Gnomad4 EAS AF: 0.0982

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.0269

Gnomad4 NFE AF: 0.0284

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0339 Hom.: 103

Bravo AF: 0.0353

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.72

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: rs2236772; hg19: chr1-20304785;