rs375318450

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000054.7(AVPR2):c.26-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000518 in 1,176,710 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.000049 ( 0 hom. 18 hem. )

Consequence

AVPR2
NM_000054.7 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.51

Publications

0 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-153905519-G-A is Benign according to our data. Variant chrX-153905519-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2964993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 9 XL,AD gene.

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	Effect	Exon Rank	Protein	UniProt
AVPR2	NM_000054.7	MANE Select	c.26-13G>A	intron	N/A	NP_000045.1	P30518-1
AVPR2	NM_001146151.3		c.26-13G>A	intron	N/A	NP_001139623.1	P30518-2
AVPR2	NR_027419.2		n.465+349G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AVPR2	ENST00000646375.2	MANE Select	c.26-13G>A	intron	N/A	ENSP00000496396.1	P30518-1
AVPR2	ENST00000337474.5	TSL:1	c.26-13G>A	intron	N/A	ENSP00000338072.5	P30518-1
AVPR2	ENST00000370049.1	TSL:1	c.26-13G>A	intron	N/A	ENSP00000359066.1	P30518-2

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

112457

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000477

AC:

AN:

125815

AF XY:

0.0000246

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000603

Gnomad OTH exome

AF:

0.000289

GnomAD4 exome

AF:

0.0000489

AC:

AN:

1064203

Hom.:

Cov.:

AF XY:

0.0000522

AC XY:

AN XY:

345131

show subpopulations

African (AFR)

AF:

0.0000394

AC:

AN:

25402

American (AMR)

AF:

0.00

AC:

AN:

30795

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18827

East Asian (EAS)

AF:

0.00

AC:

AN:

28171

South Asian (SAS)

AF:

0.0000196

AC:

AN:

50940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37403

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3247

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

824689

Other (OTH)

AF:

0.0000224

AC:

AN:

44729

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000800

AC:

AN:

112507

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34705

show subpopulations

African (AFR)

AF:

0.0000644

AC:

AN:

31052

American (AMR)

AF:

0.0000926

AC:

AN:

10798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3534

South Asian (SAS)

AF:

0.00

AC:

AN:

2761

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6217

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53065

Other (OTH)

AF:

0.00

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.75

(source)

DANN

Benign

0.54

PhyloP100

-1.5

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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