Variant chr2-159955228-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007366.5(PLA2R1):c.3272G>A(p.Gly1091Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,457,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PLA2R1
NM_007366.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18255538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2R1	NM_007366.5 linkuse as main transcript	c.3272G>A	p.Gly1091Asp	missense_variant	23/30	ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13 linkuse as main transcript	c.3272G>A	p.Gly1091Asp	missense_variant	23/30	1	NM_007366.5	P1	Q13018-1
PLA2R1	ENST00000392771.1 linkuse as main transcript	c.3272G>A	p.Gly1091Asp	missense_variant	23/27	1			Q13018-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

247348

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1457696

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

725152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.3272G>A (p.G1091D) alteration is located in exon 23 (coding exon 23) of the PLA2R1 gene. This alteration results from a G to A substitution at nucleotide position 3272, causing the glycine (G) at amino acid position 1091 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.079

Sift

Benign

0.49

T;T

Sift4G

Uncertain

0.031

D;D

Polyphen

0.97

D;D

Vest4

0.23

MutPred

0.51

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.54

MPC

0.087

ClinPred

0.040

GERP RS

3.0

Varity_R

0.027

gMVP

0.51

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

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