NM_000054.7:c.19A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000054.7(AVPR2):c.19A>T(p.Thr7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 1,209,863 control chromosomes in the GnomAD database, including 172 homozygotes. There are 1,795 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 81 hom., 730 hem., cov: 25)

Exomes 𝑓: 0.0034 ( 91 hom. 1065 hem. )

Consequence

AVPR2
NM_000054.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.473

Publications

7 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), Ambry Genetics, Orphanet
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018894374).

BP6

Variant X-153905164-A-T is Benign according to our data. Variant chrX-153905164-A-T is described in ClinVar as Benign. ClinVar VariationId is 368071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000054.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AVPR2	NM_000054.7	MANE Select	c.19A>T	p.Thr7Ser	missense	Exon 2 of 4	NP_000045.1	P30518-1
AVPR2	NM_001146151.3		c.19A>T	p.Thr7Ser	missense	Exon 2 of 3	NP_001139623.1	P30518-2
AVPR2	NR_027419.2		n.459A>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AVPR2	ENST00000646375.2	MANE Select	c.19A>T	p.Thr7Ser	missense	Exon 2 of 4	ENSP00000496396.1	P30518-1
AVPR2	ENST00000337474.5	TSL:1	c.19A>T	p.Thr7Ser	missense	Exon 1 of 3	ENSP00000338072.5	P30518-1
AVPR2	ENST00000370049.1	TSL:1	c.19A>T	p.Thr7Ser	missense	Exon 1 of 2	ENSP00000359066.1	P30518-2

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

2787

AN:

111784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0825

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00758

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000372

Gnomad FIN

AF:

0.000161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00145

Gnomad OTH

AF:

0.0287

GnomAD2 exomes

AF:

0.00773

AC:

1415

AN:

183017

AF XY:

0.00547

show subpopulations

Gnomad AFR exome

AF:

0.0845

Gnomad AMR exome

AF:

0.00463

Gnomad ASJ exome

AF:

0.00829

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00354

GnomAD4 exome

AF:

0.00345

AC:

3783

AN:

1098025

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

1065

AN XY:

363461

show subpopulations

African (AFR)

AF:

0.0814

AC:

2148

AN:

26396

American (AMR)

AF:

0.00517

AC:

182

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00841

AC:

163

AN:

19384

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30204

South Asian (SAS)

AF:

0.000240

AC:

AN:

54142

European-Finnish (FIN)

AF:

0.000123

AC:

AN:

40528

Middle Eastern (MID)

AF:

0.00244

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.00111

AC:

931

AN:

841996

Other (OTH)

AF:

0.00714

AC:

329

AN:

46076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

183

366

550

733

916

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0250

AC:

2799

AN:

111838

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

730

AN XY:

34134

show subpopulations

African (AFR)

AF:

0.0827

AC:

2541

AN:

30738

American (AMR)

AF:

0.0109

AC:

116

AN:

10687

Ashkenazi Jewish (ASJ)

AF:

0.00758

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3520

South Asian (SAS)

AF:

0.000373

AC:

AN:

2680

European-Finnish (FIN)

AF:

0.000161

AC:

AN:

6212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00145

AC:

AN:

52944

Other (OTH)

AF:

0.0283

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

103

207

310

414

517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00532

Hom.:

107

Bravo

AF:

0.0283

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0834

AC:

320

ESP6500EA

AF:

0.00282

AC:

ExAC

AF:

0.00832

AC:

1010

EpiCase

AF:

0.00120

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

AVPR2-related disorder (1)

Diabetes insipidus, nephrogenic, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.45

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.29

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

-0.47

PrimateAI

Benign

0.35

PROVEAN

Benign

0.46

REVEL

Benign

0.086

Sift

Benign

0.46

Sift4G

Benign

0.52

Polyphen

0.043

Vest4

0.028

MutPred

0.64

Gain of phosphorylation at T7 (P = 0.0696)

MVP

0.69

MPC

0.46

ClinPred

0.0045

GERP RS

-0.99

PromoterAI

-0.0079

Neutral

(source)

Varity_R

0.072

gMVP

0.56

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over