Variant X-153905288-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000054.7(AVPR2):c.25+118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 1,064,380 control chromosomes in the GnomAD database, including 386 homozygotes. There are 2,111 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 200 hom., 1113 hem., cov: 25)

Exomes 𝑓: 0.0043 ( 186 hom. 998 hem. )

Consequence

AVPR2
NM_000054.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.17

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-153905288-A-G is Benign according to our data. Variant chrX-153905288-A-G is described in ClinVar as [Benign]. Clinvar id is 1286248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
AVPR2	NM_000054.7 linkuse as main transcript	c.25+118A>G	intron_variant	ENST00000646375.2	NP_000045.1
AVPR2	NM_001146151.3 linkuse as main transcript	c.25+118A>G	intron_variant		NP_001139623.1
AVPR2	NR_027419.2 linkuse as main transcript	n.465+118A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2 linkuse as main transcript	c.25+118A>G		intron_variant			NM_000054.7	ENSP00000496396	P1	P30518-1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

4157

AN:

112310

Hom.:

200

Cov.:

AF XY:

0.0320

AC XY:

1105

AN XY:

34514

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000732

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000264

Gnomad OTH

AF:

0.0356

GnomAD4 exome

AF:

0.00426

AC:

4054

AN:

952015

Hom.:

186

AF XY:

0.00370

AC XY:

998

AN XY:

269369

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.00673

Gnomad4 ASJ exome

AF:

0.000220

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.00859

GnomAD4 genome

AF:

0.0370

AC:

4163

AN:

112365

Hom.:

200

Cov.:

AF XY:

0.0322

AC XY:

1113

AN XY:

34579

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000734

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000264

Gnomad4 OTH

AF:

0.0352

Alfa

AF:

0.0277

Hom.:

Bravo

AF:

0.0430

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.37

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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