rs35771982

chr2-160028907-G-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.898C>G(p.His300Asp) 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 1,603,876 control chromosomes in the GnomAD database, including 172,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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.

• Frequency:
  • Genomes: 𝑓 0.35 (11813 hom., cov: 32)
  • Exomes 𝑓: 0.46 (160878 hom.)
• Consequence: PLA2R1 NM_007366.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.177

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=1.1223236E-4).
• BP6: Variant 2-160028907-G-C is Benign according to our data. Variant chr2-160028907-G-C is described in ClinVar as [Benign]. Clinvar id is 1712438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2R1	NM_007366.5	c.898C>G	p.His300Asp	missense_variant	5/30	ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13	c.898C>G	p.His300Asp	missense_variant	5/30	1	NM_007366.5	P1
PLA2R1	ENST00000392771.1	c.898C>G	p.His300Asp	missense_variant	5/27	1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53694 AN: 151892 Hom.: 11811 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.342

GnomAD3 exomes AF: 0.387 AC: 97175 AN: 250908 Hom.: 21008 AF XY: 0.390 AC XY: 52929 AN XY: 135578

Gnomad AFR exome AF: 0.0916

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.314

Gnomad SAS exome AF: 0.242

Gnomad FIN exome AF: 0.510

Gnomad NFE exome AF: 0.492

Gnomad OTH exome AF: 0.409

GnomAD4 exome AF: 0.458 AC: 664970 AN: 1451864 Hom.: 160878 Cov.: 32 AF XY: 0.452 AC XY: 326770 AN XY: 722560

Gnomad4 AFR exome AF: 0.0841

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.362

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.353 AC: 53698 AN: 152012 Hom.: 11813 Cov.: 32 AF XY: 0.353 AC XY: 26226 AN XY: 74298

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.346

Alfa AF: 0.434 Hom.: 4925

Bravo AF: 0.330

TwinsUK AF: 0.487 AC: 1805

ALSPAC AF: 0.509 AC: 1960

ESP6500AA AF: 0.100 AC: 442

ESP6500EA AF: 0.488 AC: 4200

ExAC AF: 0.385 AC: 46742

Asia WGS AF: 0.316 AC: 1100 AN: 3478

EpiCase AF: 0.470

EpiControl AF: 0.464

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	0.058
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.079
Dann	Benign	0.51
DEOGEN2	Benign	0.012	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.29	T;T
MetaRNN	Benign	0.00011	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.0
Sift	Benign	0.63	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;B
Vest4		0.038
MPC		0.086
ClinPred		0.0059	T
GERP RS		-0.95
Varity_R		0.085
gMVP		0.30

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

Other links and lift over

dbSNP: rs35771982; hg19: chr2-160885418; COSMIC: COSV51775810;