Genetic Variant PLA2R1:p.Gly1106Ser (chr2-159951564-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007366.5(PLA2R1):c.3316G>A(p.Gly1106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,533,322 control chromosomes in the GnomAD database, including 163,322 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 12836 hom., cov: 32)

Exomes 𝑓: 0.45 ( 150486 hom. )

Consequence

PLA2R1
NM_007366.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.474

Publications

54 publications found

Variant links:

Genes affected

PLA2R1 (HGNC:9042): (phospholipase A2 receptor 1) This gene represents a phospholipase A2 receptor. The encoded protein likely exists as both a transmembrane form and a soluble form. The transmembrane receptor may play a role in clearance of phospholipase A2, thereby inhibiting its action. Polymorphisms at this locus have been associated with susceptibility to idiopathic membranous nephropathy. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

PLA2R1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5104307E-5).

BP6

Variant 2-159951564-C-T is Benign according to our data. Variant chr2-159951564-C-T is described in ClinVar as Benign. ClinVar VariationId is 1712437.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2R1	NM_007366.5 link	c.3316G>A	p.Gly1106Ser	missense_variant	Exon 24 of 30	ENST00000283243.13	NP_031392.3	Q13018-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2R1	ENST00000283243.13 link	c.3316G>A	p.Gly1106Ser	missense_variant	Exon 24 of 30	1	NM_007366.5	ENSP00000283243.7		Q13018-1
PLA2R1	ENST00000392771.1 link	c.3316G>A	p.Gly1106Ser	missense_variant	Exon 24 of 27	1		ENSP00000376524.1		Q13018-2

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55649

AN:

151944

Hom.:

12836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.438

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.309

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.631

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.367

GnomAD2 exomes

AF:

0.397

AC:

99601

AN:

250600

AF XY:

0.398

show subpopulations

Gnomad AFR exome

AF:

0.0930

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.271

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.452

AC:

624656

AN:

1381260

Hom.:

150486

Cov.:

AF XY:

0.447

AC XY:

308988

AN XY:

691746

show subpopulations

African (AFR)

AF:

0.0830

AC:

2720

AN:

32768

American (AMR)

AF:

0.304

AC:

13560

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

7765

AN:

25762

East Asian (EAS)

AF:

0.306

AC:

12063

AN:

39386

South Asian (SAS)

AF:

0.207

AC:

17656

AN:

85192

European-Finnish (FIN)

AF:

0.613

AC:

32706

AN:

53334

Middle Eastern (MID)

AF:

0.265

AC:

1474

AN:

5558

European-Non Finnish (NFE)

AF:

0.495

AC:

513151

AN:

1036632

Other (OTH)

AF:

0.406

AC:

23561

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

14210

28419

42629

56838

71048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14058

28116

42174

56232

70290

<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:

0.366

AC:

55656

AN:

152062

Hom.:

12836

Cov.:

AF XY:

0.367

AC XY:

27290

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.105

AC:

4338

AN:

41488

American (AMR)

AF:

0.346

AC:

5291

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1071

AN:

3468

East Asian (EAS)

AF:

0.289

AC:

1494

AN:

5174

South Asian (SAS)

AF:

0.208

AC:

999

AN:

4804

European-Finnish (FIN)

AF:

0.631

AC:

6676

AN:

10572

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34530

AN:

67958

Other (OTH)

AF:

0.369

AC:

777

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1587

3174

4762

6349

7936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.445

Hom.:

53375

Bravo

AF:

0.334

TwinsUK

AF:

0.490

AC:

1816

ALSPAC

AF:

0.518

AC:

1996

ESP6500AA

AF:

0.106

AC:

468

ESP6500EA

AF:

0.490

AC:

4216

ExAC

AF:

0.395

AC:

47957

Asia WGS

AF:

0.269

AC:

938

AN:

3478

EpiCase

AF:

0.483

EpiControl

AF:

0.477

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Atypical hemolytic-uremic syndrome

Benign:1

Oct 05, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.000015

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.46

N;N

PhyloP100

-0.47

PrimateAI

Benign

0.20

PROVEAN

Benign

0.74

N;N

REVEL

Benign

0.0010

Sift

Benign

0.81

T;T

Sift4G

Benign

0.83

T;T

Polyphen

0.0

B;B

Vest4

0.054

MPC

0.064

ClinPred

0.0040

GERP RS

-3.0

Varity_R

0.014

gMVP

0.21

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over