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NM_000054.7(AVPR2):c.410G>A (p.Arg137His) AND Nephrogenic diabetes insipidus

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 31, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV002509150.2

Allele description [Variation Report for NM_000054.7(AVPR2):c.410G>A (p.Arg137His)]

NM_000054.7(AVPR2):c.410G>A (p.Arg137His)

Gene:
AVPR2:arginine vasopressin receptor 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000054.7(AVPR2):c.410G>A (p.Arg137His)
HGVS:
  • NC_000023.11:g.153905916G>A
  • NG_008687.1:g.5943G>A
  • NG_013220.1:g.25345C>T
  • NM_000054.7:c.410G>AMANE SELECT
  • NM_001146151.3:c.410G>A
  • NP_000045.1:p.Arg137His
  • NP_001139623.1:p.Arg137His
  • LRG_716t1:c.410G>A
  • LRG_716:g.5943G>A
  • LRG_716p1:p.Arg137His
  • NC_000023.10:g.153171370G>A
  • NM_000054.4:c.410G>A
  • P30518:p.Arg137His
Protein change:
R137H; ARG137HIS
Links:
UniProtKB: P30518#VAR_003528; OMIM: 300538.0015; dbSNP: rs104894756
NCBI 1000 Genomes Browser:
rs104894756
Molecular consequence:
  • NM_000054.7:c.410G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001146151.3:c.410G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Nephrogenic diabetes insipidus
Synonyms:
Vasopressin-resistant diabetes insipidus; ADH resistant diabetes insipidus; Diabetes insipidus nephrogenic X-linked
Identifiers:
MONDO: MONDO:0016383; MedGen: C0162283; Human Phenotype Ontology: HP:0009806

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002819924Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Dec 31, 2022) 		germlineclinical testing

PubMed (24)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus.

Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, DE Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM.

J Am Soc Nephrol. 2000 Jun;11(6):1044-1054. doi: 10.1681/ASN.V1161044.

PubMed [citation]
PMID:
10820168

X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis.

Bichet DG, Arthus MF, Lonergan M, Hendy GN, Paradis AJ, Fujiwara TM, Morgan K, Gregory MC, Rosenthal W, Didwania A, et al.

J Clin Invest. 1993 Sep;92(3):1262-8.

PubMed [citation]
PMID:
8104196
PMCID:
PMC288266
See all PubMed Citations (24)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002819924.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (24)

Description

Variant summary: AVPR2 c.410G>A (p.Arg137His) results in a non-conservative amino acid change located in the GPCR, rhodopsin-like, 7TM domain (IPR017452) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.7e-06 in 176496 control chromosomes. c.410G>A has been reported in the literature in multiple individuals affected with Nephrogenic Diabetes Insipidus (example, Shoji_1998, Bichet_1993, Bichet_1994, Carroll_2006, Arthus_2000, Ashton_2018). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in the mutant receptor showing normal binding properties, but unable to stimulate the GS/adenylyl cyclase system (Barak_2001). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024