chr2-160028907-G-C

Variant names:

• chr2-160028907-G-C
• rs35771982
• NM_007366.5:c.898C>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• 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
• Publications: 56 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007366.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2R1	NM_007366.5	MANE Select	c.898C>G	p.His300Asp	missense	Exon 5 of 30	NP_031392.3
	PLA2R1	NM_001195641.2		c.898C>G	p.His300Asp	missense	Exon 5 of 30	NP_001182570.1
	PLA2R1	NM_001007267.3		c.898C>G	p.His300Asp	missense	Exon 5 of 27	NP_001007268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2R1	ENST00000283243.13	TSL:1 MANE Select	c.898C>G	p.His300Asp	missense	Exon 5 of 30	ENSP00000283243.7
	PLA2R1	ENST00000392771.1	TSL:1	c.898C>G	p.His300Asp	missense	Exon 5 of 27	ENSP00000376524.1

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

GnomAD2 exomes AF: 0.387 AC: 97175 AN: 250908 AF XY: 0.390

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 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

African (AFR) AF: 0.0841 AC: 2813 AN: 33434

American (AMR) AF: 0.301 AC: 13449 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 7295 AN: 26086

East Asian (EAS) AF: 0.362 AC: 14338 AN: 39660

South Asian (SAS) AF: 0.243 AC: 20897 AN: 86078

European-Finnish (FIN) AF: 0.506 AC: 27018 AN: 53392

Middle Eastern (MID) AF: 0.250 AC: 1436 AN: 5754

European-Non Finnish (NFE) AF: 0.501 AC: 552514 AN: 1102674

Other (OTH) AF: 0.419 AC: 25210 AN: 60108

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

African (AFR) AF: 0.102 AC: 4245 AN: 41474

American (AMR) AF: 0.335 AC: 5108 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 955 AN: 3458

East Asian (EAS) AF: 0.329 AC: 1704 AN: 5172

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4818

European-Finnish (FIN) AF: 0.520 AC: 5477 AN: 10530

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33836 AN: 67972

Other (OTH) AF: 0.346 AC: 731 AN: 2114

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

Oct 05, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.00011	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.18
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.0
Sift	Benign	0.63	T
Sift4G	Benign	0.73	T
Polyphen		0.0	B
Vest4		0.038
MPC		0.086
ClinPred		0.0059	T
GERP RS		-0.95
Varity_R		0.085
gMVP		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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