2-159955228-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007366.5(PLA2R1):c.3272G>A(p.Gly1091Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,457,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PLA2R1 NM_007366.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.524

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18255538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2R1	NM_007366.5	c.3272G>A	p.Gly1091Asp	missense_variant	23/30	ENST00000283243.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2R1	ENST00000283243.13	c.3272G>A	p.Gly1091Asp	missense_variant	23/30	1	NM_007366.5	P1
PLA2R1	ENST00000392771.1	c.3272G>A	p.Gly1091Asp	missense_variant	23/27	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000364 AC: 9 AN: 247348 Hom.: 0 AF XY: 0.0000374 AC XY: 5 AN XY: 133702

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1457696 Hom.: 0 Cov.: 28 AF XY: 0.0000276 AC XY: 20 AN XY: 725152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.0000996

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.3272G>A (p.G1091D) alteration is located in exon 23 (coding exon 23) of the PLA2R1 gene. This alteration results from a G to A substitution at nucleotide position 3272, causing the glycine (G) at amino acid position 1091 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	19
Dann	Benign	0.95
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.061
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.21	N;N
REVEL	Benign	0.079
Sift	Benign	0.49	T;T
Sift4G	Uncertain	0.031	D;D
Polyphen		0.97	D;D
Vest4		0.23
MutPred		0.51		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.54
MPC		0.087
ClinPred		0.040	T
GERP RS		3.0
Varity_R		0.027
gMVP		0.51

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: rs778997231; hg19: chr2-160811739; COSMIC: COSV51775644;