dbSNP rs2307246: PLA2G2A:c.185+16C>T (chr1-19978364-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.284

Publications

17 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

PLA2G2A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001395463.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLA2G2A	NM_001395463.1	MANE Select	c.185+16C>T	intron	N/A	NP_001382392.1	P14555
PLA2G2A	NM_000300.4		c.185+16C>T	intron	N/A	NP_000291.1	P14555
PLA2G2A	NM_001161727.2		c.185+16C>T	intron	N/A	NP_001155199.1	P14555

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLA2G2A	ENST00000482011.3	TSL:1 MANE Select	c.185+16C>T	intron	N/A	ENSP00000504762.1	P14555
PLA2G2A	ENST00000375111.7	TSL:1	c.185+16C>T	intron	N/A	ENSP00000364252.3	P14555
PLA2G2A	ENST00000400520.8	TSL:1	c.185+16C>T	intron	N/A	ENSP00000383364.3	P14555

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26736

AN:

152064

Hom.:

2795

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.207

AC XY:

149821

AN XY:

724520

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

10964

21929

32893

43858

54822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8308

16616

24924

33232

41540

<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:

0.176

AC:

26757

AN:

152182

Hom.:

2800

Cov.:

AF XY:

0.173

AC XY:

12900

AN XY:

74410

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16070

AN:

67994

Other (OTH)

AF:

0.175

AC:

368

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1106

2212

3319

4425

5531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.204

Hom.:

4366

Bravo

AF:

0.161

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.38

PhyloP100

-0.28

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over