rs56689668
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_000054.7(AVPR2):c.26-6T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 1.0 ( 38892 hom., 33978 hem., cov: 24)
Exomes 𝑓: 1.0 ( 360821 hom. 349485 hem. )
Failed GnomAD Quality Control
Consequence
AVPR2
NM_000054.7 splice_region, splice_polypyrimidine_tract, intron
NM_000054.7 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01070
2
Clinical Significance
Conservation
PhyloP100: -0.0360
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant X-153905526-T-G is Benign according to our data. Variant chrX-153905526-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 254772.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153905526-T-G is described in Lovd as [Benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AVPR2 | NM_000054.7 | c.26-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000646375.2 | |||
AVPR2 | NM_001146151.3 | c.26-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
AVPR2 | NR_027419.2 | n.465+356T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AVPR2 | ENST00000646375.2 | c.26-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_000054.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 111732AN: 111762Hom.: 38897 Cov.: 24 AF XY: 1.00 AC XY: 33916AN XY: 33922 FAILED QC
GnomAD3 genomes
?
AF:
AC:
111732
AN:
111762
Hom.:
Cov.:
24
AF XY:
AC XY:
33916
AN XY:
33922
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.999 AC: 130924AN: 131006Hom.: 44689 AF XY: 0.999 AC XY: 41491AN XY: 41518
GnomAD3 exomes
AF:
AC:
130924
AN:
131006
Hom.:
AF XY:
AC XY:
41491
AN XY:
41518
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 1071431AN: 1071907Hom.: 360821 Cov.: 43 AF XY: 1.00 AC XY: 349485AN XY: 349645
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
AC:
1071431
AN:
1071907
Hom.:
Cov.:
43
AF XY:
AC XY:
349485
AN XY:
349645
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 111784AN: 111814Hom.: 38892 Cov.: 24 AF XY: 1.00 AC XY: 33978AN XY: 33984
GnomAD4 genome
?
Data not reliable, filtered out with message: InbreedingCoeff
AF:
AC:
111784
AN:
111814
Hom.:
Cov.:
24
AF XY:
AC XY:
33978
AN XY:
33984
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 03, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 02, 2016 | This is a RefSeq error. The reference base (c.26-6T) is the minor allele. This a llele (T) has been identified in 0.78% (22/2806) of East Asian chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs56 689668) and thus meets criteria to be classified as likely benign. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Diabetes insipidus, nephrogenic, X-linked Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Diabetes insipidus, nephrogenic, X-linked;C1845202:Nephrogenic syndrome of inappropriate antidiuresis Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 19, 2017 | - - |
Nephrogenic syndrome of inappropriate antidiuresis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -18
Find out detailed SpliceAI scores and Pangolin per-transcript scores at