rs5201
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000054.7(AVPR2):āc.927A>Gā(p.Leu309=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,204,137 control chromosomes in the GnomAD database, including 66,424 homozygotes. There are 147,760 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.51 ( 12623 hom., 17014 hem., cov: 23)
Exomes š: 0.35 ( 53801 hom. 130746 hem. )
Consequence
AVPR2
NM_000054.7 synonymous
NM_000054.7 synonymous
Scores
1
1
10
Clinical Significance
Conservation
PhyloP100: 2.37
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=1.3549908E-6).
BP6
Variant X-153906539-A-G is Benign according to our data. Variant chrX-153906539-A-G is described in ClinVar as [Benign]. Clinvar id is 254775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153906539-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=2.37 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AVPR2 | NM_000054.7 | c.927A>G | p.Leu309= | synonymous_variant | 4/4 | ENST00000646375.2 | |
AVPR2 | NM_001146151.3 | c.*103A>G | 3_prime_UTR_variant | 3/3 | |||
AVPR2 | NR_027419.2 | n.880A>G | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AVPR2 | ENST00000646375.2 | c.927A>G | p.Leu309= | synonymous_variant | 4/4 | NM_000054.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.510 AC: 56442AN: 110772Hom.: 12615 Cov.: 23 AF XY: 0.513 AC XY: 16956AN XY: 33032
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GnomAD3 exomes AF: 0.475 AC: 83957AN: 176633Hom.: 16385 AF XY: 0.457 AC XY: 28242AN XY: 61855
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GnomAD4 exome AF: 0.355 AC: 387930AN: 1093309Hom.: 53801 Cov.: 36 AF XY: 0.364 AC XY: 130746AN XY: 359545
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GnomAD4 genome AF: 0.510 AC: 56508AN: 110828Hom.: 12623 Cov.: 23 AF XY: 0.514 AC XY: 17014AN XY: 33098
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 26, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Diabetes insipidus, nephrogenic, X-linked Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at