chr2-160028931-T-C

Variant names:

• chr2-160028931-T-C
• rs3749117
• NM_007366.5:c.874A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. 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. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). 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
• Publications: 52 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 -10 ACMG points.

• BP6: Variant 2-160028931-T-C is Benign according to our data. Variant chr2-160028931-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.874A>G	p.Met292Val	missense	Exon 5 of 30	NP_031392.3
	PLA2R1	NM_001195641.2		c.874A>G	p.Met292Val	missense	Exon 5 of 30	NP_001182570.1
	PLA2R1	NM_001007267.3		c.874A>G	p.Met292Val	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.874A>G	p.Met292Val	missense	Exon 5 of 30	ENSP00000283243.7
	PLA2R1	ENST00000392771.1	TSL:1	c.874A>G	p.Met292Val	missense	Exon 5 of 27	ENSP00000376524.1

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

GnomAD2 exomes AF: 0.390 AC: 97730 AN: 250708 AF XY: 0.392

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 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

African (AFR) AF: 0.108 AC: 3598 AN: 33388

American (AMR) AF: 0.304 AC: 13591 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7352 AN: 26004

East Asian (EAS) AF: 0.361 AC: 14321 AN: 39634

South Asian (SAS) AF: 0.243 AC: 20845 AN: 85874

European-Finnish (FIN) AF: 0.506 AC: 26995 AN: 53354

Middle Eastern (MID) AF: 0.286 AC: 1644 AN: 5744

European-Non Finnish (NFE) AF: 0.500 AC: 544911 AN: 1089828

Other (OTH) AF: 0.422 AC: 25147 AN: 59650

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

African (AFR) AF: 0.124 AC: 5144 AN: 41476

American (AMR) AF: 0.340 AC: 5190 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1708 AN: 5172

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4816

European-Finnish (FIN) AF: 0.519 AC: 5482 AN: 10554

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33892 AN: 67968

Other (OTH) AF: 0.354 AC: 747 AN: 2110

Alfa AF: 0.440 Hom.: 62077

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

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	0.12
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
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.2
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.79	N
REVEL	Benign	0.10
Sift	Benign	0.091	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.11
MPC		0.067
ClinPred		0.013	T
GERP RS		4.6
Varity_R		0.15
gMVP		0.42
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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