1-19979394-C-A

Variant names:

• chr1-19979394-C-A
• rs3753827
• NM_001395463.1:c.-107+186G>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.-107+186G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,996 control chromosomes in the GnomAD database, including 13,194 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 0.41 (13194 hom., cov: 32)
• Consequence: PLA2G2A NM_001395463.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395463.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2A	NM_001395463.1	MANE Select	c.-107+186G>T		intron	N/A	NP_001382392.1
	PLA2G2A	NM_000300.4		c.-107+186G>T		intron	N/A	NP_000291.1
	PLA2G2A	NM_001161727.2		c.-107+186G>T		intron	N/A	NP_001155199.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2A	ENST00000482011.3	TSL:1 MANE Select	c.-107+186G>T		intron	N/A	ENSP00000504762.1
	PLA2G2A	ENST00000375111.7	TSL:1	c.-107+186G>T		intron	N/A	ENSP00000364252.3
	PLA2G2A	ENST00000400520.8	TSL:1	c.-139+186G>T		intron	N/A	ENSP00000383364.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62572 AN: 151878 Hom.: 13193 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.412 AC: 62584 AN: 151996 Hom.: 13194 Cov.: 32 AF XY: 0.410 AC XY: 30429 AN XY: 74264

African (AFR) AF: 0.359 AC: 14861 AN: 41442

American (AMR) AF: 0.405 AC: 6195 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1509 AN: 3468

East Asian (EAS) AF: 0.409 AC: 2107 AN: 5156

South Asian (SAS) AF: 0.496 AC: 2386 AN: 4806

European-Finnish (FIN) AF: 0.366 AC: 3868 AN: 10558

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30013 AN: 67972

Other (OTH) AF: 0.435 AC: 918 AN: 2110

Alfa AF: 0.433 Hom.: 27227

Bravo AF: 0.413

Asia WGS AF: 0.448 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.64
PhyloP100		0.27
PromoterAI		-0.26	Neutral
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: rs3753827; hg19: chr1-20305887;