rs2307246

Variant names:

• chr1-19978364-G-A
• rs2307246
• NM_001395463.1:c.185+16C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• colorectal cancer

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.185+16C>T		intron_variant	Intron 3 of 4	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.185+16C>T		intron_variant	Intron 3 of 4	1	NM_001395463.1	ENSP00000504762.1

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

GnomAD2 exomes AF: 0.175 AC: 43559 AN: 248664 AF XY: 0.177

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 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

African (AFR) AF: 0.103 AC: 3445 AN: 33402

American (AMR) AF: 0.0944 AC: 4218 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 3481 AN: 26014

East Asian (EAS) AF: 0.0185 AC: 732 AN: 39636

South Asian (SAS) AF: 0.123 AC: 10586 AN: 85984

European-Finnish (FIN) AF: 0.254 AC: 13338 AN: 52424

Middle Eastern (MID) AF: 0.168 AC: 805 AN: 4792

European-Non Finnish (NFE) AF: 0.230 AC: 255566 AN: 1109632

Other (OTH) AF: 0.190 AC: 11426 AN: 60152

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

African (AFR) AF: 0.105 AC: 4377 AN: 41526

American (AMR) AF: 0.136 AC: 2087 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3468

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5182

South Asian (SAS) AF: 0.106 AC: 509 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2547 AN: 10586

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16070 AN: 67994

Other (OTH) AF: 0.175 AC: 368 AN: 2108

Alfa AF: 0.204 Hom.: 4366

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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