rs3749117

chr2-160028931-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007366.5(PLA2R1):c.874A>G(p.Met292Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 1,590,182 control chromosomes in the GnomAD database, including 171,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M292T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.36 (11993 hom., cov: 32)
  • Exomes 𝑓: 0.46 (159433 hom.)
• Consequence: PLA2R1 NM_007366.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.21

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0010646284).
• BP6: Variant 2-160028931-T-C is Benign according to our data. Variant chr2-160028931-T-C is described in ClinVar as [Benign]. Clinvar id is 1712439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2R1	NM_007366.5	c.874A>G	p.Met292Val	missense_variant	5/30	ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13	c.874A>G	p.Met292Val	missense_variant	5/30	1	NM_007366.5	P1
PLA2R1	ENST00000392771.1	c.874A>G	p.Met292Val	missense_variant	5/27	1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54781 AN: 151934 Hom.: 11990 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.390 AC: 97730 AN: 250708 Hom.: 21150 AF XY: 0.392 AC XY: 53178 AN XY: 135498

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.314

Gnomad SAS exome AF: 0.243

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.458 AC: 658404 AN: 1438128 Hom.: 159433 Cov.: 30 AF XY: 0.452 AC XY: 323950 AN XY: 716418

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.360 AC: 54790 AN: 152054 Hom.: 11993 Cov.: 32 AF XY: 0.360 AC XY: 26740 AN XY: 74318

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.354

Alfa AF: 0.449 Hom.: 30465

Bravo AF: 0.338

TwinsUK AF: 0.487 AC: 1806

ALSPAC AF: 0.508 AC: 1958

ESP6500AA AF: 0.121 AC: 534

ESP6500EA AF: 0.490 AC: 4212

ExAC AF: 0.388 AC: 47079

Asia WGS AF: 0.320 AC: 1112 AN: 3478

EpiCase AF: 0.472

EpiControl AF: 0.466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atypical hemolytic-uremic syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Oct 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	15
Dann	Benign	0.90
DEOGEN2	Benign	0.039	T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.79	N;N
REVEL	Benign	0.10
Sift	Benign	0.091	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.0020	B;B
Vest4		0.11
MPC		0.067
ClinPred		0.013	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.43		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.43		Position offset: 32

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

Publications

LitVar

Other links and lift over

dbSNP: rs3749117; hg19: chr2-160885442; COSMIC: COSV51787759;