rs10758325

chr9-35804152-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003995.4(NPR2):c.1887+1349G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,928 control chromosomes in the GnomAD database, including 10,299 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 0.35 (10299 hom., cov: 32)
• Consequence: NPR2 NM_003995.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

Genes affected

NPR2 (HGNC:7944): (natriuretic peptide receptor 2) This gene encodes natriuretic peptide receptor B, one of two integral membrane receptors for natriuretic peptides. Both NPR1 and NPR2 contain five functional domains: an extracellular ligand-binding domain, a single membrane-spanning region, and intracellularly a protein kinase homology domain, a helical hinge region involved in oligomerization, and a carboxyl-terminal guanylyl cyclase catalytic domain. The protein is the primary receptor for C-type natriuretic peptide (CNP), which upon ligand binding exhibits greatly increased guanylyl cyclase activity. Mutations in this gene are the cause of acromesomelic dysplasia Maroteaux type. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPR2	NM_003995.4	c.1887+1349G>A		intron_variant		ENST00000342694.7
NPR2	NM_001378923.1	c.1896+1349G>A		intron_variant
NPR2	XM_024447561.2	c.483+1349G>A		intron_variant
NPR2	XM_047423431.1	c.492+1349G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPR2	ENST00000342694.7	c.1887+1349G>A		intron_variant		1	NM_003995.4	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53848 AN: 151812 Hom.: 10292 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.374

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 53864 AN: 151928 Hom.: 10299 Cov.: 32 AF XY: 0.355 AC XY: 26317 AN XY: 74234

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.374

Alfa AF: 0.413 Hom.: 12986

Bravo AF: 0.343

Asia WGS AF: 0.354 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.0
Dann	Benign	0.58

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: rs10758325; hg19: chr9-35804149; COSMIC: COSV61042638; COSMIC: COSV61042638;