rs2148911

Positions:

• chr1-20069094-G-A
• chr1-20069094-G-T

Variant summary

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

The XM_005245891.6(PLA2G5):​c.83+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 467,400 control chromosomes in the GnomAD database, including 2,092 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 0.062 (488 hom., cov: 32)
  • Exomes 𝑓: 0.085 (1604 hom.)
• Consequence: PLA2G5 XM_005245891.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

Genes affected

PLA2G5 (HGNC:9038): (phospholipase A2 group V) This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PLA2G5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G5	XM_005245891.6	c.83+62G>A		intron_variant			XP_005245948.1
PLA2G5	XM_005245892.6	c.83+62G>A		intron_variant			XP_005245949.1
PLA2G5	XM_011541586.4	c.83+62G>A		intron_variant			XP_011539888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G5	ENST00000460175.5	n.497+62G>A		intron_variant		3
PLA2G5	ENST00000465698.5	n.501+62G>A		intron_variant		3
PLA2G5	ENST00000469069.5	n.524+62G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9512 AN: 152084 Hom.: 491 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0539

Gnomad OTH AF: 0.0578

GnomAD4 exome AF: 0.0850 AC: 26799 AN: 315198 Hom.: 1604 AF XY: 0.0889 AC XY: 15870 AN XY: 178462

Gnomad4 AFR exome AF: 0.0181

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0594

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0624 AC: 9500 AN: 152202 Hom.: 488 Cov.: 32 AF XY: 0.0673 AC XY: 5007 AN XY: 74402

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0539

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0466 Hom.: 76

Bravo AF: 0.0632

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.80
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2148911; hg19: chr1-20395587; COSMIC: COSV64282876;