rs782021693

Variant names:

• chrX-153905551-TCTGCCCAGC-T
• rs782021693
• NM_000054.7:c.55_63delCTGCCCAGC

Your query was ambiguous. Multiple possible variants found:

• chrX-153905551-TCTGCCCAGC-T
• chrX-153905551-TCTGCCCAGC-TCTGCCCAGCCTGCCCAGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM2 PM4 BS2

The NM_000054.7(AVPR2):​c.55_63delCTGCCCAGC​(p.Leu19_Ser21del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000462 in 1,081,346 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: AVPR2 NM_000054.7 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.98
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000054.7.
• BS2: High AC in GnomAdExome4 at 5 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVPR2	NM_000054.7	c.55_63delCTGCCCAGC	p.Leu19_Ser21del	conservative_inframe_deletion	Exon 3 of 4	ENST00000646375.2	NP_000045.1
AVPR2	NM_001146151.3	c.55_63delCTGCCCAGC	p.Leu19_Ser21del	conservative_inframe_deletion	Exon 3 of 3		NP_001139623.1
AVPR2	NR_027419.2	n.465+391_465+399delCTGCCCAGC		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVPR2	ENST00000646375.2	c.55_63delCTGCCCAGC	p.Leu19_Ser21del	conservative_inframe_deletion	Exon 3 of 4		NM_000054.7	ENSP00000496396.1
ENSG00000284987	ENST00000646191.1	n.96+3510_96+3518delGCTGGGCAG		intron_variant	Intron 1 of 4			ENSP00000493873.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000209 AC: 3 AN: 143711 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000818

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000888

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000462 AC: 5 AN: 1081346 Hom.: 0 AF XY: 0.00000283 AC XY: 1 AN XY: 352892

African (AFR) AF: 0.00 AC: 0 AN: 25949

American (AMR) AF: 0.00 AC: 0 AN: 33146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19066

East Asian (EAS) AF: 0.00 AC: 0 AN: 29193

South Asian (SAS) AF: 0.00 AC: 0 AN: 52281

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3749

European-Non Finnish (NFE) AF: 0.00000599 AC: 5 AN: 834067

Other (OTH) AF: 0.00 AC: 0 AN: 45362

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=199/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs782021693; hg19: chrX-153171005;