X-153904993-G-GC

Variant names:

• chrX-153904993-G-GC
• rs55712963
• ENST00000434679.6:n.-153_-152insC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000054.7(AVPR2):​c.-153_-152insC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (38920 hom., 33922 hem., cov: 0)
  • Exomes 𝑓: 1.0 (237173 hom. 208764 hem.)
  • Failed GnomAD Quality Control
• Consequence: AVPR2 NM_000054.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13
• Publications: 4 publications found

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

ENSG00000284987 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-153904993-G-GC is Benign according to our data. Variant chrX-153904993-G-GC is described in ClinVar as [Benign]. Clinvar id is 1289944.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR2	NM_000054.7	c.-153_-152insC		5_prime_UTR_variant	Exon 2 of 4	ENST00000646375.2	NP_000045.1
AVPR2	NR_027419.2	n.288_289insC		non_coding_transcript_exon_variant	Exon 2 of 4
AVPR2	NM_001146151.3	c.-153_-152insC		5_prime_UTR_variant	Exon 2 of 3		NP_001139623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2	c.-153_-152insC		5_prime_UTR_variant	Exon 2 of 4		NM_000054.7	ENSP00000496396.1
ENSG00000284987	ENST00000646191.1	n.96+4076_96+4077insG		intron_variant	Intron 1 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 111707 AN: 111708 Hom.: 38925 Cov.: 0

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD2 exomes AF: 1.00 AC: 168451 AN: 168457 AF XY: 1.00

Gnomad AFR exome AF: 1.00

Gnomad AMR exome AF: 1.00

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 683122 AN: 683143 Hom.: 237173 Cov.: 12 AF XY: 1.00 AC XY: 208764 AN XY: 208773

African (AFR) AF: 1.00 AC: 18175 AN: 18175

American (AMR) AF: 1.00 AC: 34393 AN: 34394

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 16716 AN: 16716

East Asian (EAS) AF: 1.00 AC: 28075 AN: 28076

South Asian (SAS) AF: 1.00 AC: 46019 AN: 46032

European-Finnish (FIN) AF: 1.00 AC: 36066 AN: 36066

Middle Eastern (MID) AF: 1.00 AC: 2593 AN: 2593

European-Non Finnish (NFE) AF: 1.00 AC: 468679 AN: 468685

Other (OTH) AF: 1.00 AC: 32406 AN: 32406

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 111762 AN: 111763 Hom.: 38920 Cov.: 0 AF XY: 1.00 AC XY: 33922 AN XY: 33923

African (AFR) AF: 1.00 AC: 30693 AN: 30693

American (AMR) AF: 1.00 AC: 10663 AN: 10663

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2645 AN: 2645

East Asian (EAS) AF: 1.00 AC: 3526 AN: 3526

South Asian (SAS) AF: 1.00 AC: 2704 AN: 2705

European-Finnish (FIN) AF: 1.00 AC: 6037 AN: 6037

Middle Eastern (MID) AF: 1.00 AC: 218 AN: 218

European-Non Finnish (NFE) AF: 1.00 AC: 53071 AN: 53071

Other (OTH) AF: 1.00 AC: 1520 AN: 1520

Alfa AF: 1.00 Hom.: 12694

Asia WGS AF: 1.00 AC: 2522 AN: 2522

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55712963; hg19: chrX-153170447; COSMIC: COSV61685727; COSMIC: COSV61685727;