chr2-159987112-T-C

Variant names:

• chr2-159987112-T-C
• rs6757188
• NM_007366.5:c.2037+44A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007366.5(PLA2R1):​c.2037+44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,420,604 control chromosomes in the GnomAD database, including 41,884 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4129 hom., cov: 32)
  • Exomes 𝑓: 0.24 (37755 hom.)
• Consequence: PLA2R1 NM_007366.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 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.2037+44A>G		intron	N/A	NP_031392.3
	PLA2R1	NM_001195641.2		c.2037+44A>G		intron	N/A	NP_001182570.1	B7ZML4
	PLA2R1	NM_001007267.3		c.2037+44A>G		intron	N/A	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.2037+44A>G		intron	N/A	ENSP00000283243.7	Q13018-1
	PLA2R1	ENST00000392771.1	TSL:1	c.2037+44A>G		intron	N/A	ENSP00000376524.1	Q13018-2
	PLA2R1	ENST00000890090.1		c.2037+44A>G		intron	N/A	ENSP00000560149.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33245 AN: 151992 Hom.: 4123 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.271

GnomAD2 exomes AF: 0.256 AC: 63594 AN: 248632 AF XY: 0.250

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.231

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.237 AC: 300129 AN: 1268494 Hom.: 37755 Cov.: 18 AF XY: 0.236 AC XY: 150832 AN XY: 640314

African (AFR) AF: 0.132 AC: 3891 AN: 29412

American (AMR) AF: 0.456 AC: 20144 AN: 44218

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 8630 AN: 24766

East Asian (EAS) AF: 0.255 AC: 9877 AN: 38706

South Asian (SAS) AF: 0.216 AC: 17726 AN: 82236

European-Finnish (FIN) AF: 0.154 AC: 8180 AN: 53280

Middle Eastern (MID) AF: 0.231 AC: 1227 AN: 5314

European-Non Finnish (NFE) AF: 0.232 AC: 217235 AN: 936644

Other (OTH) AF: 0.245 AC: 13219 AN: 53918

GnomAD4 genome AF: 0.219 AC: 33266 AN: 152110 Hom.: 4129 Cov.: 32 AF XY: 0.216 AC XY: 16055 AN XY: 74360

African (AFR) AF: 0.136 AC: 5644 AN: 41486

American (AMR) AF: 0.380 AC: 5803 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1427 AN: 5168

South Asian (SAS) AF: 0.212 AC: 1022 AN: 4820

European-Finnish (FIN) AF: 0.139 AC: 1467 AN: 10592

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15695 AN: 67982

Other (OTH) AF: 0.269 AC: 569 AN: 2114

Alfa AF: 0.242 Hom.: 1945

Bravo AF: 0.236

Asia WGS AF: 0.256 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6757188; hg19: chr2-160843623; COSMIC: COSV51779643;