Genetic Variant NM_001395463.1:c.*230C>T (chr1-19975471-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.*230C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 585,588 control chromosomes in the GnomAD database, including 4,993 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 ( 1010 hom., cov: 32)

Exomes 𝑓: 0.13 ( 3983 hom. )

Consequence

PLA2G2A
NM_001395463.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390

Publications

22 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=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1 link	c.*230C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3 link	c.*230C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_001395463.1	ENSP00000504762.1		P14555

Frequencies

GnomAD3 genomes

AF:

0.0992

AC:

15084

AN:

152102

Hom.:

1011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0940

GnomAD4 exome

AF:

0.128

AC:

55515

AN:

433368

Hom.:

3983

Cov.:

AF XY:

0.131

AC XY:

30075

AN XY:

229438

show subpopulations

African (AFR)

AF:

0.0230

AC:

278

AN:

12096

American (AMR)

AF:

0.195

AC:

3594

AN:

18388

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

1578

AN:

13196

East Asian (EAS)

AF:

0.187

AC:

5533

AN:

29566

South Asian (SAS)

AF:

0.178

AC:

8118

AN:

45728

European-Finnish (FIN)

AF:

0.106

AC:

3046

AN:

28854

Middle Eastern (MID)

AF:

0.160

AC:

300

AN:

1870

European-Non Finnish (NFE)

AF:

0.116

AC:

30088

AN:

258664

Other (OTH)

AF:

0.119

AC:

2980

AN:

25006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2469

4937

7406

9874

12343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.0990

AC:

15074

AN:

152220

Hom.:

1010

Cov.:

AF XY:

0.104

AC XY:

7726

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0235

AC:

975

AN:

41532

American (AMR)

AF:

0.164

AC:

2502

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

423

AN:

3472

East Asian (EAS)

AF:

0.174

AC:

900

AN:

5186

South Asian (SAS)

AF:

0.182

AC:

875

AN:

4820

European-Finnish (FIN)

AF:

0.125

AC:

1322

AN:

10584

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.114

AC:

7762

AN:

68016

Other (OTH)

AF:

0.0930

AC:

196

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

683

1366

2049

2732

3415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.112

Hom.:

3566

Bravo

AF:

0.0996

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

(source)

DANN

Benign

0.53

PhyloP100

0.39

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