Renal tubulopathies
Gene: AVPR2
Comment on mode of pathogenicity: Gain of function variantsCreated: 14 Oct 2021, 4:14 p.m. | Last Modified: 14 Oct 2021, 4:14 p.m.
Panel Version: 2.29
Comment on mode of pathogenicity: From Emma Ashton - NSIAD caused by gain of function mutations (mainly codon 137)Created: 8 Oct 2019, 3:06 p.m. | Last Modified: 8 Oct 2019, 3:06 p.m.
Panel Version: 1.192
Note: left mode of inheritance as X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males as there are reports of heterozygous females with NDI due to X-inactivation.Created: 8 Oct 2019, 2:51 p.m. | Last Modified: 8 Oct 2019, 2:51 p.m.
Panel Version: 1.191
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: AVPR2; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided; Other Comments: Skewed X-inactivation may result in NDI manifesting females (reports on OMIM). NSIAD caused by gain of function mutations (mainly codon 137)Created: 3 Feb 2019, 11:32 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Nephrogenic diabetes insipidus MIM 304800; Nephrogenic syndrome of inappropriate antidiuresis MIM 300539
Mode of pathogenicity
Other - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Promoted to Green.Created: 22 Nov 2018, 12:54 p.m.
Added this gene from the Monogenic nephrogenic diabetes insipidus (Version 1.8, code 18) gene panel, after request from the Genomics England Clinical Team. There are >3 unrelated cases/families reported. PMID: 9329382 indicates that heterozygous females may be affected, depending on X-linked skewing. The 'treatable' tag was added due to information available on Orphanet regarding Nephrogenic diabetes insipidus: "Patients should receive a low salt diet with limited potassium and protein intake and take thiazide diuretics in combination with indomethacin. This treatment has changed the life of affected patients, especially infants." summary reviewed by : Dr Patrick NIAUDET - Last update: February 2007 (http://www.orpha.net).
Sources: OtherCreated: 22 Nov 2018, 12:52 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation)
Publications
Tag Skewed X-inactivation tag was added to gene: AVPR2.
Phenotypes for gene: AVPR2 were changed from Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation); Nephrogenic syndrome of inappropriate antidiuresis, 300539 to Diabetes insipidus, nephrogenic, OMIM:304800; Nephrogenic syndrome of inappropriate antidiuresis, OMIM:300539
Mode of pathogenicity for gene: AVPR2 was changed from Other to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of pathogenicity for gene: AVPR2 was changed from None to Other
Phenotypes for gene: AVPR2 were changed from Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation) to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation); Nephrogenic syndrome of inappropriate antidiuresis, 300539
Source NHS GMS was added to AVPR2. Rating Changed from Green List (high evidence) to Green List (high evidence)
Gene: avpr2 has been classified as Green List (High Evidence).
gene: AVPR2 was added gene: AVPR2 was added to Renal tubulopathies. Sources: Other treatable tags were added to gene: AVPR2. Mode of inheritance for gene: AVPR2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: AVPR2 were set to 18726898; 27565746; 27117808; 26974133; 26828532 Phenotypes for gene: AVPR2 were set to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation)