Variant 2-159945031-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007366.5(PLA2R1):c.4019G>T(p.Gly1340Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

PLA2R1
NM_007366.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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:

PLA2R1 (HGNC:):

PLA2R1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2R1	NM_007366.5 linkuse as main transcript	c.4019G>T	p.Gly1340Val	missense_variant	28/30	ENST00000283243.13	NP_031392.3	Q13018-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2R1	ENST00000283243.13 linkuse as main transcript	c.4019G>T	p.Gly1340Val	missense_variant	28/30	1	NM_007366.5	ENSP00000283243.7		Q13018-1
PLA2R1	ENST00000460710.2 linkuse as main transcript	n.-31G>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727006

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Apr 26, 2023

The c.4019G>T (p.G1340V) alteration is located in exon 28 (coding exon 28) of the PLA2R1 gene. This alteration results from a G to T substitution at nucleotide position 4019, causing the glycine (G) at amino acid position 1340 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.81

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.21

Sift

Uncertain

0.0080

Sift4G

Benign

0.23

Polyphen

1.0

Vest4

0.76

MutPred

0.57

Loss of disorder (P = 0.025);

MVP

0.30

MPC

0.37

ClinPred

0.97

GERP RS

4.9

Varity_R

0.39

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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