1-19978572-C-T

Variant names:

• chr1-19978572-C-T
• rs10732279
• NM_001395463.1:c.41-48G>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.41-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 1,610,808 control chromosomes in the GnomAD database, including 479,292 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 0.78 (46489 hom., cov: 32)
  • Exomes 𝑓: 0.77 (432803 hom.)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.41-48G>A		intron_variant	Intron 2 of 4	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.41-48G>A		intron_variant	Intron 2 of 4	1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118482 AN: 151978 Hom.: 46466 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.781

GnomAD2 exomes AF: 0.787 AC: 196689 AN: 249796 AF XY: 0.790

Gnomad AFR exome AF: 0.804

Gnomad AMR exome AF: 0.805

Gnomad ASJ exome AF: 0.848

Gnomad EAS exome AF: 0.945

Gnomad FIN exome AF: 0.746

Gnomad NFE exome AF: 0.742

Gnomad OTH exome AF: 0.787

GnomAD4 exome AF: 0.769 AC: 1121699 AN: 1458712 Hom.: 432803 Cov.: 36 AF XY: 0.771 AC XY: 559424 AN XY: 725774

African (AFR) AF: 0.803 AC: 26866 AN: 33448

American (AMR) AF: 0.800 AC: 35756 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 22088 AN: 26118

East Asian (EAS) AF: 0.942 AC: 37387 AN: 39692

South Asian (SAS) AF: 0.840 AC: 72393 AN: 86180

European-Finnish (FIN) AF: 0.736 AC: 38340 AN: 52126

Middle Eastern (MID) AF: 0.805 AC: 4354 AN: 5408

European-Non Finnish (NFE) AF: 0.754 AC: 837329 AN: 1110772

Other (OTH) AF: 0.783 AC: 47186 AN: 60286

GnomAD4 genome AF: 0.779 AC: 118556 AN: 152096 Hom.: 46489 Cov.: 32 AF XY: 0.783 AC XY: 58184 AN XY: 74356

African (AFR) AF: 0.799 AC: 33156 AN: 41488

American (AMR) AF: 0.790 AC: 12071 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2952 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4873 AN: 5166

South Asian (SAS) AF: 0.860 AC: 4143 AN: 4820

European-Finnish (FIN) AF: 0.749 AC: 7925 AN: 10578

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50811 AN: 67972

Other (OTH) AF: 0.781 AC: 1647 AN: 2108

Alfa AF: 0.761 Hom.: 22748

Bravo AF: 0.788

Asia WGS AF: 0.882 AC: 3068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.42
PhyloP100		-1.6
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: rs10732279; hg19: chr1-20305065;