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Skeletal dysplasia

Gene: NPR3

Amber List (moderate evidence)

NPR3 (natriuretic peptide receptor 3)
EnsemblGeneIds (GRCh38): ENSG00000113389
EnsemblGeneIds (GRCh37): ENSG00000113389
OMIM: 108962, Gene2Phenotype
NPR3 is in 4 panels

2 reviews

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Promoting this gene from grey to amber with a recommendation for green rating following GMS review. 3 unrelated cases with a similar phenotype and supporting functional data and mouse model.
Created: 21 Jan 2021, 4:43 p.m. | Last Modified: 21 Jan 2021, 4:43 p.m.
Panel Version: 2.75
PMID: 30032985 Boudin et al 2018 - report 4 individuals from 3 unrelated families (1 Dutch, 1 Pakistani, 1 unknown ancestry) presenting with tall stature, long digits, and extra epiphyses in the hands and feet. WES was used in 2 families and targeted NPR3 screening in the third. Biallelic variants were found in NPR3 in all affected individuals. In one family 2 affected individuals were compound heterozygous for a missense and nonsense variant. The other two individuals were homozygous for missense and frameshift variants. The variants segregated with the phenotype in all 3 families. All variants were either not reported or appear at low frequency in dbSNP, ExAC and gnomAD databases and never in the homozyous state. Functional studies show that 3 of the variants either result in NMD or absent localization at the plasma membrane.

PMID: 10468599 Jaubert 1999 - analysis of mouse strains that have elongated bodies show that in each have mutations in the Npr3 gene.
Created: 21 Jan 2021, 4:41 p.m. | Last Modified: 21 Jan 2021, 4:41 p.m.
Panel Version: 2.73

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

4 individuals in 3 families reported with striking phenotypic similarity.
Functional evidence compelling.
Mouse model recapitulates phenotype (including skeletal features).
Sources: Literature
Created: 19 Feb 2020, 6:54 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Tall stature; arachnodactyly; extra epiphyses; aortic dilatation

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Tall stature
  • arachnodactyly
  • extra epiphyses
  • aortic dilatation
Tags
for-review
OMIM
108962
Clinvar variants
Variants in NPR3
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

21 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: npr3 has been classified as Amber List (Moderate Evidence).

21 Jan 2021, Gel status: 0

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: NPR3 were set to PMID: 30032985; 10468599

21 Jan 2021, Gel status: 0

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: NPR3.

19 Feb 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Ian Berry (Leeds Genetics Laboratory)

gene: NPR3 was added gene: NPR3 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NPR3 were set to PMID: 30032985; 10468599 Phenotypes for gene: NPR3 were set to Tall stature; arachnodactyly; extra epiphyses; aortic dilatation Penetrance for gene: NPR3 were set to unknown Review for gene: NPR3 was set to GREEN gene: NPR3 was marked as current diagnostic