Genetic Variant 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

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:

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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 id is 3257628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2D	NM_012400.4 link	c.133G>A	p.Gly45Ser	missense_variant	Exon 2 of 4	ENST00000375105.8	NP_036532.1	Q9UNK4-1
PLA2G2D	NM_001271814.2 link	c.133G>A	p.Gly45Ser	missense_variant	Exon 2 of 3		NP_001258743.1	Q9UNK4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2D	ENST00000375105.8 link	c.133G>A	p.Gly45Ser	missense_variant	Exon 2 of 4	1	NM_012400.4	ENSP00000364246.3		Q9UNK4-1
PLA2G2D	ENST00000617227.1 link	c.133G>A	p.Gly45Ser	missense_variant	Exon 2 of 3	1		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

Gnomad4 AFR exome

AF:

0.00116

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00159

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00689

AC:

180

AN:

26136

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000104

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00288

AC:

154

AN:

53420

Gnomad4 NFE exome

AF:

0.00764

AC:

8498

AN:

1111972

Gnomad4 Remaining exome

AF:

0.00596

AC:

360

AN:

60394

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Gnomad4 AFR

AF:

0.00120

AC:

0.00120331

AN:

0.00120331

Gnomad4 AMR

AF:

0.00150

AC:

0.00150346

AN:

0.00150346

Gnomad4 ASJ

AF:

0.00691

AC:

0.00691244

AN:

0.00691244

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00217

AC:

0.00216695

AN:

0.00216695

Gnomad4 NFE

AF:

0.00628

AC:

0.00627701

AN:

0.00627701

Gnomad4 OTH

AF:

0.00189

AC:

0.00189036

AN:

0.00189036

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PLA2G2D: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

T;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.078

T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Pathogenic

4.4

H;.

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.9

D;.

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over