2-159951564-C-T

Variant names:

• chr2-159951564-C-T
• rs3828323
• NM_007366.5:c.3316G>A

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

• 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
• Publications: 54 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=1.5104307E-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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2R1	NM_007366.5	MANE Select	c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 30	NP_031392.3
	PLA2R1	NM_001195641.2		c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 30	NP_001182570.1	B7ZML4
	PLA2R1	NM_001007267.3		c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 27	NP_001007268.1	Q13018-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2R1	ENST00000283243.13	TSL:1 MANE Select	c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 30	ENSP00000283243.7	Q13018-1
	PLA2R1	ENST00000392771.1	TSL:1	c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 27	ENSP00000376524.1	Q13018-2
	PLA2R1	ENST00000890090.1		c.3316G>A	p.Gly1106Ser	missense	Exon 24 of 30	ENSP00000560149.1

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

GnomAD2 exomes AF: 0.397 AC: 99601 AN: 250600 AF XY: 0.398

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 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

African (AFR) AF: 0.0830 AC: 2720 AN: 32768

American (AMR) AF: 0.304 AC: 13560 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7765 AN: 25762

East Asian (EAS) AF: 0.306 AC: 12063 AN: 39386

South Asian (SAS) AF: 0.207 AC: 17656 AN: 85192

European-Finnish (FIN) AF: 0.613 AC: 32706 AN: 53334

Middle Eastern (MID) AF: 0.265 AC: 1474 AN: 5558

European-Non Finnish (NFE) AF: 0.495 AC: 513151 AN: 1036632

Other (OTH) AF: 0.406 AC: 23561 AN: 57990

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

African (AFR) AF: 0.105 AC: 4338 AN: 41488

American (AMR) AF: 0.346 AC: 5291 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1494 AN: 5174

South Asian (SAS) AF: 0.208 AC: 999 AN: 4804

European-Finnish (FIN) AF: 0.631 AC: 6676 AN: 10572

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34530 AN: 67958

Other (OTH) AF: 0.369 AC: 777 AN: 2104

Alfa AF: 0.445 Hom.: 53375

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Atypical hemolytic-uremic syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.47
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.0010
Sift	Benign	0.81	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.054
MPC		0.064
ClinPred		0.0040	T
GERP RS		-3.0
Varity_R		0.014
gMVP		0.21
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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