VCV000017830.6 - ClinVar

NM_000486.6(AQP2):c.190G>A (p.Gly64Arg)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000486.6(AQP2):c.190G>A (p.Gly64Arg)

Variation ID: 17830 Accession: VCV000017830.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q13.12 12: 49951020 (GRCh38) [ NCBI UCSC ] 12: 50344803 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Dec 31, 2022	Mar 10, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000486.6:c.190G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000477.1:p.Gly64Arg	missense
NC_000012.12:g.49951020G>A
NC_000012.11:g.50344803G>A
NG_008913.1:g.5280G>A
LRG_717:g.5280G>A
LRG_717t1:c.190G>A	LRG_717p1:p.Gly64Arg
	P41181:p.Gly64Arg

... more HGVS ... less HGVS

Protein change

G64R

Other names

Canonical SPDI

NC_000012.12:49951019:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Exome Aggregation Consortium (ExAC) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00002

Links

OMIM: 107777.0004 dbSNP: rs104894326 ClinGen: CA127468 UniProtKB: P41181#VAR_004401 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
AQP2		-	-	GRCh38 GRCh37	130	397

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely pathogenic (1)	criteria provided, single submitter	Mar 17, 2017	RCV000518067.2
Nephrogenic diabetes insipidus	Likely pathogenic (1)	no assertion criteria provided	Sep 16, 2020	RCV001274488.1
Diabetes insipidus, nephrogenic, autosomal	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Mar 10, 2022	RCV001375962.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Mar 10, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Diabetes insipidus, nephrogenic, autosomal Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002797044.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Jun 20, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Diabetes insipidus, nephrogenic, autosomal (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Genomic Medicine Lab, University of California San Francisco Study: CSER-P3EGS Accession: SCV001572954.1 First in ClinVar: May 05, 2021 Last updated: May 05, 2021	Sex: female
Likely pathogenic (Mar 17, 2017)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000612401.1 First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017	Publications: PubMed (4) PubMed: 7524315‚ 11374071‚ 7537761‚ 8793791
Likely pathogenic (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Nephrogenic diabetes insipidus Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001458715.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Pathogenic (Oct 01, 1994)	no assertion criteria provided Method: literature only	DIABETES INSIPIDUS, NEPHROGENIC, 2, AUTOSOMAL RECESSIVE Affected status: not provided Allele origin: germline	OMIM Accession: SCV000039698.3 First in ClinVar: Apr 04, 2013 Last updated: Jun 26, 2021	Publications: PubMed (1) PubMed: 7524315 Comment on evidence: In an Italian patient with nephrogenic diabetes insipidus (NDI2; 125800) whose parents were consanguineous, van Lieburg et al. (1994) identified a homozygous 190G-A transition in … (more) In an Italian patient with nephrogenic diabetes insipidus (NDI2; 125800) whose parents were consanguineous, van Lieburg et al. (1994) identified a homozygous 190G-A transition in exon 1 of the AQP2 gene, resulting in a gly64-to-arg (G64R) substitution. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Functionality of aquaporin-2 missense mutants in recessive nephrogenic diabetes insipidus.	Marr N	Pflugers Archiv : European journal of physiology	2001	PMID: 11374071
Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus.	Deen PM	Journal of the American Society of Nephrology : JASN	1996	PMID: 8793791
Water channels encoded by mutant aquaporin-2 genes in nephrogenic diabetes insipidus are impaired in their cellular routing.	Deen PM	The Journal of clinical investigation	1995	PMID: 7537761
Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene.	van Lieburg AF	American journal of human genetics	1994	PMID: 7524315

Text-mined citations for rs104894326 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 08, 2024

ClinVar Genomic variation as it relates to human health

NM_000486.6(AQP2):c.190G>A (p.Gly64Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs104894326 ...