Genetic Variant PLA2G2A:c.-180C>G (chr1-19979653-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000375111.7(PLA2G2A):c.-180C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,400 control chromosomes in the GnomAD database, including 3,082 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 0.19 ( 3076 hom., cov: 33)

Exomes 𝑓: 0.23 ( 6 hom. )

Consequence

PLA2G2A
ENST00000375111.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.90

Publications

34 publications found

Variant links:

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)

PLA2G2A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1 link	c.-180C>G		upstream_gene_variant		ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3 link	c.-180C>G		upstream_gene_variant		1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28556

AN:

152052

Hom.:

3070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.226

AC:

AN:

230

Hom.:

Cov.:

AF XY:

0.225

AC XY:

AN XY:

142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.225

AC:

AN:

138

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.271

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28585

AN:

152170

Hom.:

3076

Cov.:

AF XY:

0.185

AC XY:

13740

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.137

AC:

5679

AN:

41518

American (AMR)

AF:

0.140

AC:

2137

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

601

AN:

3470

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5176

South Asian (SAS)

AF:

0.104

AC:

504

AN:

4832

European-Finnish (FIN)

AF:

0.254

AC:

2680

AN:

10566

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16268

AN:

67996

Other (OTH)

AF:

0.185

AC:

392

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1162

2325

3487

4650

5812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.232

Hom.:

576

Bravo

AF:

0.174

Asia WGS

AF:

0.0810

AC:

280

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.087

(source)

DANN

Benign

0.43

PhyloP100

-1.9

PromoterAI

0.071

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over