X-153905164-A-T

Position:

chrX-153905164-A-T

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AVPR2	NM_000054.7 linkuse as main transcript	c.19A>T	p.Thr7Ser	missense_variant	2/4	ENST00000646375.2	NP_000045.1
AVPR2	NM_001146151.3 linkuse as main transcript	c.19A>T	p.Thr7Ser	missense_variant	2/3		NP_001139623.1
AVPR2	NR_027419.2 linkuse as main transcript	n.459A>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2 linkuse as main transcript	c.19A>T	p.Thr7Ser	missense_variant	2/4		NM_000054.7	ENSP00000496396	P1	P30518-1

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

2787

AN:

111784

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

724

AN XY:

34070

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

GnomAD3 exomes

AF:

0.00773

AC:

1415

AN:

183017

Hom.:

AF XY:

0.00547

AC XY:

370

AN XY:

67587

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 SAS exome

AF:

0.000314

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

Gnomad4 AFR exome

AF:

0.0814

Gnomad4 AMR exome

AF:

0.00517

Gnomad4 ASJ exome

AF:

0.00841

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.000123

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.0250

AC:

2799

AN:

111838

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

730

AN XY:

34134

show subpopulations

Gnomad4 AFR

AF:

0.0827

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00758

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000373

Gnomad4 FIN

AF:

0.000161

Gnomad4 NFE

AF:

0.00145

Gnomad4 OTH

AF:

0.0283

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

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Diabetes insipidus, nephrogenic, X-linked

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

AVPR2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.45

DANN

Benign

0.75

DEOGEN2

Benign

0.29

T;T;.;T;.

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.41

.;.;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

0.46

.;N;N;N;N

REVEL

Benign

0.086

Sift

Benign

0.46

.;T;T;T;T

Sift4G

Benign

0.52

.;T;T;T;T

Polyphen

0.043

B;B;.;B;B

Vest4

0.028, 0.048, 0.059

MutPred

0.64

Gain of phosphorylation at T7 (P = 0.0696);Gain of phosphorylation at T7 (P = 0.0696);Gain of phosphorylation at T7 (P = 0.0696);Gain of phosphorylation at T7 (P = 0.0696);Gain of phosphorylation at T7 (P = 0.0696);

MVP

0.69

MPC

0.46

ClinPred

0.0045

GERP RS

-0.99

Varity_R

0.072

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over