chrX-153905518-C-T

Variant names:

• chrX-153905518-C-T
• rs781795563
• NM_000054.7:c.26-14C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000054.7(AVPR2):​c.26-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,174,932 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.000023 (0 hom. 8 hem.)
• Consequence: AVPR2 NM_000054.7 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.744
• Publications: 0 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-153905518-C-T is Benign according to our data. Variant chrX-153905518-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2972617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 24 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR2	NM_000054.7	c.26-14C>T		intron_variant	Intron 2 of 3	ENST00000646375.2	NP_000045.1
AVPR2	NM_001146151.3	c.26-14C>T		intron_variant	Intron 2 of 2		NP_001139623.1
AVPR2	NR_027419.2	n.465+348C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2	c.26-14C>T		intron_variant	Intron 2 of 3		NM_000054.7	ENSP00000496396.1
ENSG00000284987	ENST00000646191.1	n.96+3552G>A		intron_variant	Intron 1 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112614 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000482 AC: 6 AN: 124442 AF XY: 0.0000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000416

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000204

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 24 AN: 1062318 Hom.: 0 Cov.: 29 AF XY: 0.0000233 AC XY: 8 AN XY: 344026

African (AFR) AF: 0.00 AC: 0 AN: 25323

American (AMR) AF: 0.0000326 AC: 1 AN: 30637

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18801

East Asian (EAS) AF: 0.000143 AC: 4 AN: 28068

South Asian (SAS) AF: 0.0000197 AC: 1 AN: 50862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37309

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3225

European-Non Finnish (NFE) AF: 0.0000206 AC: 17 AN: 823419

Other (OTH) AF: 0.0000224 AC: 1 AN: 44674

GnomAD4 genome AF: 0.00000888 AC: 1 AN: 112614 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34772

African (AFR) AF: 0.00 AC: 0 AN: 31029

American (AMR) AF: 0.00 AC: 0 AN: 10805

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6241

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53108

Other (OTH) AF: 0.00 AC: 0 AN: 1516

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		-0.74
PromoterAI		0.042	Neutral
Mutation Taster		=100/0	polymorphism

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: rs781795563; hg19: chrX-153170972;