chr1-19975708-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001395463.1(PLA2G2A):c.428G>A(p.Arg143His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,613,616 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 42 hom. )

Consequence

PLA2G2A
NM_001395463.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.45

Publications

13 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008064479).

BP6

Variant 1-19975708-C-T is Benign according to our data. Variant chr1-19975708-C-T is described in ClinVar as Benign. ClinVar VariationId is 3038442.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 655 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA2G2A	NM_001395463.1	MANE Select	c.428G>A	p.Arg143His	missense	Exon 5 of 5	NP_001382392.1	P14555
PLA2G2A	NM_000300.4		c.428G>A	p.Arg143His	missense	Exon 6 of 6	NP_000291.1	P14555
PLA2G2A	NM_001161727.2		c.428G>A	p.Arg143His	missense	Exon 6 of 6	NP_001155199.1	P14555

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA2G2A	ENST00000482011.3	TSL:1 MANE Select	c.428G>A	p.Arg143His	missense	Exon 5 of 5	ENSP00000504762.1	P14555
PLA2G2A	ENST00000375111.7	TSL:1	c.428G>A	p.Arg143His	missense	Exon 6 of 6	ENSP00000364252.3	P14555
PLA2G2A	ENST00000400520.8	TSL:1	c.428G>A	p.Arg143His	missense	Exon 5 of 5	ENSP00000383364.3	P14555

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

655

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00726

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00465

AC:

1169

AN:

251482

AF XY:

0.00489

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00735

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00684

AC:

9996

AN:

1461430

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

4854

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33472

American (AMR)

AF:

0.00288

AC:

129

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.00451

AC:

389

AN:

86248

European-Finnish (FIN)

AF:

0.00139

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00804

AC:

8938

AN:

1111594

Other (OTH)

AF:

0.00623

AC:

376

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

443

887

1330

1774

2217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.00430

AC:

655

AN:

152186

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

278

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41502

American (AMR)

AF:

0.00301

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00291

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00726

AC:

494

AN:

68004

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00618

Hom.:

Bravo

AF:

0.00434

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00593

AC:

ExAC

AF:

0.00477

AC:

579

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00533

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PLA2G2A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.1

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.13

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.52

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

PhyloP100

-2.4

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.3

REVEL

Benign

0.030

Sift

Uncertain

0.014

Sift4G

Benign

0.14

Polyphen

0.78

Vest4

0.10

MVP

0.25

MPC

0.73

ClinPred

0.012

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.19

Mutation Taster

=97/3

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over