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Skeletal dysplasia

Gene: NPR2

Green List (high evidence)

NPR2 (natriuretic peptide receptor 2)
EnsemblGeneIds (GRCh38): ENSG00000159899
EnsemblGeneIds (GRCh37): ENSG00000159899
OMIM: 108961, Gene2Phenotype
NPR2 is in 7 panels

5 reviews

Mehdi Montazer (Mashhad University of Medical Sciences)

Green List (high evidence)

A new paper from Turkey.
Created: 6 Jan 2021, 8:18 a.m. | Last Modified: 6 Jan 2021, 8:18 a.m.
Panel Version: 2.42

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Acromesomelic dysplasia, Maroteaux type (OMIM: # 602875)

Publications

  • https://doi.org/10.1038/s10038-020-00871-0

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

acromesomelic dysplasias, Overgrowth (tall stature) syndromes with skeletal involvement. Several cases; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acromesomelic dysplasia, Maroteaux type 602875; Epiphyseal chondrodysplasia, Miura type 615923; Short stature with nonspecific skeletal abnormalities 616255

Eleanor Williams (Genomics England Curator)

I don't know

Comment on mode of inheritance: Leaving the MOI as both, because there are both AD and AR inheritances associated with different types of skeletal dysplasia in OMIM.
Created: 21 Jan 2021, 12:14 p.m. | Last Modified: 21 Jan 2021, 12:14 p.m.
Panel Version: 2.71
PMID: 33288834 - Simsek-Kiper et al 2020 - they investigated 26 AMDM patients from 22 unrelated families. Sanger sequencing of NPR2 was performed in 23 patients and exome sequencing was performed in 5 patients They found
NPR2 variants in 23 patients (19 were homozygotes, 4 were compound heterozygotes). 22 distinct NPR2 (NM_003995) variants (14 missense, 5 nonsense, 2 intronic, and 1 single-amino acid deletion) were detected. In 14 families, segregation analysis was performed and showed the heterozygous NPR2 carrier status of the parents. Detailed radiographic evaluations were done, showing osteopenia, shortness in long tubular bones, radial bowing and radial head dislocation in the majority of cases. Other phenotypic features included motor developmental delay (11/23), global developmental delay/intellectual disability (GDD/ID) (5/23), spinal canal stenosis (2/23), and atlantoaxial dislocation (1/23), renal abnormalities and oligodontia. However, the authors note that the high level of parental consanguinity (18 patients) might have contributed to these phenotypes, from other gene variants.
The height of carrier parents was also assessed and found to be significantly lower than controls.
Created: 21 Jan 2021, 11:01 a.m. | Last Modified: 21 Jan 2021, 11:01 a.m.
Panel Version: 2.70
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NPR2; Initial rating suggestion: green
Created: 6 Mar 2019, 11:36 a.m.

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Listed as associated with Skeletal Dysplasia by Gene Advisor (June 2016), Steve Abbs
Created: 27 Jul 2016, 9:49 a.m.
Comment when marking as ready: Associated with phenotypes in G2P. Numerous variants reported in these phenotypes.
Created: 12 Jul 2016, 10:31 a.m.
Comment on list classification: Used diagnostically by Ana Beleza (Guy's and St Thomas' NHS Foundation Trust)
Created: 21 Jun 2016, 12:59 p.m.

Ana Beleza (Bristol Regional Genetics Service)

Green List (high evidence)

Tier 1
Created: 17 Jun 2016, 8:06 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Acromesomelic dysplasia, Maroteaux type 602875; Epiphyseal chondrodysplasia, Miura type 615923; Short stature with nonspecific skeletal abnormalities 616255

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Expert list
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • Acromesomelic dysplasia, Maroteaux type 602875
  • Short stature with nonspecific skeletal abnormalities 616255
  • Epiphyseal chondrodysplasia, Miura type 615923
OMIM
108961
Clinvar variants
Variants in NPR2
Penetrance
Complete
Panels with this gene

History Filter Activity

21 Jan 2021, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: NPR2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

6 May 2019, Gel status: 4

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes Acromesomelic dysplasia, Maroteaux type 602875; Short stature with nonspecific skeletal abnormalities 616255; Epiphyseal chondrodysplasia, Miura type 615923 for gene: NPR2

6 Mar 2019, Gel status: 3

Added New Source, Status Update

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to NPR2. Rating Changed from Green List (high evidence) to Green List (high evidence)

9 Aug 2016, Gel status: 4

panel promoted to version 1

Sarah Leigh (Genomics England Curator)

Promoted to version 1 9th August 2016

12 Jul 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

12 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NPR2 were set to Acromesomelic dysplasia, Maroteaux type 602875; Epiphyseal chondrodysplasia, Miura type 615923; Short stature with nonspecific skeletal abnormalities 616255

12 Jul 2016, Gel status: 4

Upload gene information

Sarah Leigh (Genomics England Curator)

NPR2 was added to Unexplained skeletal dysplasiapanel. Sources: Emory Genetics Laboratory,Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN

12 Jul 2016, Gel status: 4

Upload gene information

Sarah Leigh (Genomics England Curator)

NPR2 was added to Unexplained skeletal dysplasiapanel. Sources: Emory Genetics Laboratory,Expert list,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,UKGTN

8 Jul 2016, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for NPR2 was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

8 Jul 2016, Gel status: 4

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for NPR2 were set to Acromesomelic dysplasia, Maroteaux type 602875; Epiphyseal chondrodysplasia, Miura type 615923; Short stature with nonspecific skeletal abnormalities 616255

21 Jun 2016, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

18 May 2016, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

NPR2 was added to Unexplained skeletal dysplasiapanel. Sources:

18 May 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

NPR2 was created by sleigh