rs5201

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000054.7(AVPR2):c.927A>G(p.Leu309Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,204,137 control chromosomes in the GnomAD database, including 66,424 homozygotes. There are 147,760 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 12623 hom., 17014 hem., cov: 23)

Exomes 𝑓: 0.35 ( 53801 hom. 130746 hem. )

Consequence

AVPR2
NM_000054.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 2.37

Publications

20 publications found

Variant links:

Genes affected

AVPR2 (HGNC:897): (arginine vasopressin receptor 2) This gene encodes the vasopressin receptor, type 2, also known as the V2 receptor, which belongs to the seven-transmembrane-domain G protein-coupled receptor (GPCR) superfamily, and couples to Gs thus stimulating adenylate cyclase. The subfamily that includes the V2 receptor, the V1a and V1b vasopressin receptors, the oxytocin receptor, and isotocin and mesotocin receptors in non-mammals, is well conserved, though several members signal via other G proteins. All bind similar cyclic nonapeptide hormones. The V2 receptor is expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts, where its primary property is to respond to the pituitary hormone arginine vasopressin (AVP) by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of this gene is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. The V2 receptor is also expressed outside the kidney although its tissue localization is uncertain. When these 'extrarenal receptors' are stimulated by infusion of a V2 selective agonist (dDAVP), a variety of clotting factors are released into the bloodstream. The physiologic importance of this property is not known - its absence does not appear to be detrimental in NDI patients. The gene expression has also been described in fetal lung tissue and lung cancer associated with alternative splicing. [provided by RefSeq, Jul 2008]

AVPR2 Gene-Disease associations (from GenCC):

diabetes insipidus, nephrogenic, X-linked
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
nephrogenic syndrome of inappropriate antidiuresis
Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
nephrogenic diabetes insipidus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

AVPR2 links:

ENSG00000284987 (HGNC:):

ENSG00000284987 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3549908E-6).

BP6

Variant X-153906539-A-G is Benign according to our data. Variant chrX-153906539-A-G is described in ClinVar as [Benign]. Clinvar id is 254775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR2	NM_000054.7 link	c.927A>G	p.Leu309Leu	synonymous_variant	Exon 4 of 4	ENST00000646375.2	NP_000045.1	P30518-1
AVPR2	NR_027419.2 link	n.880A>G		non_coding_transcript_exon_variant	Exon 4 of 4
AVPR2	NM_001146151.3 link	c.*103A>G		3_prime_UTR_variant	Exon 3 of 3		NP_001139623.1	P30518-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2 link	c.927A>G	p.Leu309Leu	synonymous_variant	Exon 4 of 4		NM_000054.7	ENSP00000496396.1		P30518-1
ENSG00000284987	ENST00000646191.1 link	n.96+2531T>C		intron_variant	Intron 1 of 4			ENSP00000493873.1		A0A2R8Y4P6

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

56442

AN:

110772

Hom.:

12615

Cov.:

show subpopulations

Gnomad AFR

AF:

0.865

Gnomad AMI

AF:

0.0784

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.709

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.485

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.518

GnomAD2 exomes

AF:

0.475

AC:

83957

AN:

176633

AF XY:

0.457

show subpopulations

Gnomad AFR exome

AF:

0.875

Gnomad AMR exome

AF:

0.683

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.355

AC:

387930

AN:

1093309

Hom.:

53801

Cov.:

AF XY:

0.364

AC XY:

130746

AN XY:

359545

show subpopulations

African (AFR)

AF:

0.878

AC:

23107

AN:

26326

American (AMR)

AF:

0.674

AC:

23498

AN:

34866

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

6957

AN:

19024

East Asian (EAS)

AF:

0.716

AC:

21592

AN:

30138

South Asian (SAS)

AF:

0.704

AC:

37514

AN:

53293

European-Finnish (FIN)

AF:

0.313

AC:

12615

AN:

40324

Middle Eastern (MID)

AF:

0.512

AC:

2102

AN:

4103

European-Non Finnish (NFE)

AF:

0.288

AC:

241666

AN:

839374

Other (OTH)

AF:

0.412

AC:

18879

AN:

45861

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

10319

20638

30957

41276

51595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9156

18312

27468

36624

45780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.510

AC:

56508

AN:

110828

Hom.:

12623

Cov.:

AF XY:

0.514

AC XY:

17014

AN XY:

33098

show subpopulations

African (AFR)

AF:

0.865

AC:

26405

AN:

30524

American (AMR)

AF:

0.599

AC:

6311

AN:

10533

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

913

AN:

2631

East Asian (EAS)

AF:

0.708

AC:

2453

AN:

3465

South Asian (SAS)

AF:

0.718

AC:

1918

AN:

2672

European-Finnish (FIN)

AF:

0.319

AC:

1887

AN:

5921

Middle Eastern (MID)

AF:

0.463

AC:

100

AN:

216

European-Non Finnish (NFE)

AF:

0.298

AC:

15679

AN:

52687

Other (OTH)

AF:

0.525

AC:

789

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

773

1546

2318

3091

3864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.393

Hom.:

20550

Bravo

AF:

0.546

TwinsUK

AF:

0.290

AC:

1077

ALSPAC

AF:

0.292

AC:

843

ESP6500AA

AF:

0.857

AC:

3287

ESP6500EA

AF:

0.300

AC:

2018

ExAC

AF:

0.471

AC:

57094

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 26, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diabetes insipidus, nephrogenic, X-linked

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrogenic syndrome of inappropriate antidiuresis

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.1

(source)

DANN

Benign

0.85

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.27

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-1.1

PhyloP100

2.4

PROVEAN

Pathogenic

-7.5

REVEL

Benign

0.26

Sift

Benign

0.23

Sift4G

Uncertain

0.042

ClinPred

0.038

GERP RS

3.4

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over