dbSNP rs139125782: PLA2G2D:p.Gly45Ser (chr1-20116385-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_012400.4(PLA2G2D):c.133G>A(p.Gly45Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00612 in 1,614,144 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 37 hom. )

Consequence

PLA2G2D
NM_012400.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.55

Publications

10 publications found

Variant links:

Genes affected

PLA2G2D (HGNC:9033): (phospholipase A2 group IID) This gene encodes a secreted member of the phospholipase A2 family, and is found in a cluster of related family members on chromosome 1. Phospholipase A2 family members hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce lysophospholipids and free fatty acid. This gene may be involved in inflammation and immune response, and in weight loss associated with chronic obstructive pulmonary disease. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

PLA2G2D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07836455).

BP6

Variant 1-20116385-C-T is Benign according to our data. Variant chr1-20116385-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3257628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 37 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012400.4. 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
	PLA2G2D	NM_012400.4	MANE Select	c.133G>A	p.Gly45Ser	missense	Exon 2 of 4	NP_036532.1	Q9UNK4-1
	PLA2G2D	NM_001271814.2		c.133G>A	p.Gly45Ser	missense	Exon 2 of 3	NP_001258743.1	Q9UNK4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	ENST00000375105.8	TSL:1 MANE Select	c.133G>A	p.Gly45Ser	missense	Exon 2 of 4	ENSP00000364246.3	Q9UNK4-1
	PLA2G2D	ENST00000617227.1	TSL:1	c.133G>A	p.Gly45Ser	missense	Exon 2 of 3	ENSP00000482871.1	Q9UNK4-2

Frequencies

GnomAD3 genomes

AF:

0.00365

AC:

555

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00402

AC:

1012

AN:

251450

AF XY:

0.00397

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00698

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00638

AC:

9326

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00612

AC XY:

4450

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

33480

American (AMR)

AF:

0.00159

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00689

AC:

180

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00288

AC:

154

AN:

53420

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00764

AC:

8498

AN:

1111972

Other (OTH)

AF:

0.00596

AC:

360

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.00364

AC:

555

AN:

152294

Hom.:

Cov.:

AF XY:

0.00306

AC XY:

228

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41552

American (AMR)

AF:

0.00150

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00628

AC:

427

AN:

68026

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00571

Hom.:

Bravo

AF:

0.00371

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00674

AC:

ExAC

AF:

0.00442

AC:

537

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00551

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.056

MetaRNN

Benign

0.078

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

4.4

PhyloP100

4.5

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.93

MVP

0.84

MPC

0.27

ClinPred

0.13

GERP RS

5.3

Varity_R

0.93

gMVP

0.74

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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