2-159951564-C-T

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.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. 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 0.37 (12836 hom., cov: 32)
  • Exomes 𝑓: 0.45 (150486 hom.)
• Consequence: PLA2R1 NM_007366.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.474

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=1.5104307E-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 id 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/exons	MANE	UniProt
PLA2R1	NM_007366.5	c.3316G>A	p.Gly1106Ser	missense_variant	24/30	ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13	c.3316G>A	p.Gly1106Ser	missense_variant	24/30	1	NM_007366.5	P1
PLA2R1	ENST00000392771.1	c.3316G>A	p.Gly1106Ser	missense_variant	24/27	1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55649 AN: 151944 Hom.: 12836 Cov.: 32

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

GnomAD3 exomes AF: 0.397 AC: 99601 AN: 250600 Hom.: 22908 AF XY: 0.398 AC XY: 53916 AN XY: 135462

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 SAS exome AF: 0.208

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.: 24 AF XY: 0.447 AC XY: 308988 AN XY: 691746

Gnomad4 AFR exome AF: 0.0830

Gnomad4 AMR exome AF: 0.304

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.613

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.366 AC: 55656 AN: 152062 Hom.: 12836 Cov.: 32 AF XY: 0.367 AC XY: 27290 AN XY: 74316

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.369

Alfa AF: 0.462 Hom.: 40936

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

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	0.060
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.34
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.000015	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.46	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.20	T
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	T
GERP RS		-3.0
Varity_R		0.014
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs3828323; hg19: chr2-160808075; COSMIC: COSV51775114;