rs955587

Variant names:

• chr1-19976658-C-T
• rs955587
• NM_001395463.1:c.293-815G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395463.1(PLA2G2A):​c.293-815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0993 in 152,156 control chromosomes in the GnomAD database, including 1,006 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 0.099 (1006 hom., cov: 32)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.293-815G>A		intron_variant	Intron 4 of 4	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.293-815G>A		intron_variant	Intron 4 of 4	1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15125 AN: 152038 Hom.: 1006 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0793

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0943

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0993 AC: 15115 AN: 152156 Hom.: 1006 Cov.: 32 AF XY: 0.104 AC XY: 7734 AN XY: 74402

African (AFR) AF: 0.0237 AC: 983 AN: 41528

American (AMR) AF: 0.163 AC: 2485 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3468

East Asian (EAS) AF: 0.174 AC: 901 AN: 5170

South Asian (SAS) AF: 0.177 AC: 854 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1311 AN: 10596

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7844 AN: 67976

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.109 Hom.: 449

Bravo AF: 0.100

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.60
DANN	Benign	0.75
PhyloP100		-1.0
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: rs955587; hg19: chr1-20303151;