1-19979653-G-C

Position:

• chr1-19979653-G-C

Variant summary

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

The NM_000300.4(PLA2G2A):​c.-180C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,400 control chromosomes in the GnomAD database, including 3,082 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 0.19 (3076 hom., cov: 33)
  • Exomes 𝑓: 0.23 (6 hom.)
• Consequence: PLA2G2A NM_000300.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.-180C>G		upstream_gene_variant		ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.-180C>G		upstream_gene_variant		1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28556 AN: 152052 Hom.: 3070 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.226 AC: 52 AN: 230 Hom.: 6 Cov.: 0 AF XY: 0.225 AC XY: 32 AN XY: 142

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.167

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.188 AC: 28585 AN: 152170 Hom.: 3076 Cov.: 33 AF XY: 0.185 AC XY: 13740 AN XY: 74376

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.185

Alfa AF: 0.232 Hom.: 576

Bravo AF: 0.174

Asia WGS AF: 0.0810 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.087
DANN	Benign	0.43

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: rs11573156; hg19: chr1-20306146; COSMIC: COSV64287002; COSMIC: COSV64287002;