1-19975434-A-T

Position:

• chr1-19975434-A-T

Variant summary

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

The NM_001161729.1(PLA2G2A):​c.*267T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 508,038 control chromosomes in the GnomAD database, including 7,168 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 (2693 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4475 hom.)
• Consequence: PLA2G2A NM_001161729.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.*267T>A		downstream_gene_variant		ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.*267T>A		downstream_gene_variant		1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27785 AN: 152012 Hom.: 2686 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.154 AC: 54645 AN: 355908 Hom.: 4475 Cov.: 0 AF XY: 0.150 AC XY: 28348 AN XY: 188422

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.183 AC: 27842 AN: 152130 Hom.: 2693 Cov.: 32 AF XY: 0.183 AC XY: 13579 AN XY: 74378

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0807 Hom.: 104

Bravo AF: 0.194

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.80

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: rs876018; hg19: chr1-20301927;