rs3741559
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_000486.6(AQP2):c.360+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,600,584 control chromosomes in the GnomAD database, including 30,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 2535 hom., cov: 33)
Exomes 𝑓: 0.19 ( 28003 hom. )
Consequence
AQP2
NM_000486.6 splice_donor_region, intron
NM_000486.6 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00003329
2
Clinical Significance
Conservation
PhyloP100: 1.58
Genes affected
AQP2 (HGNC:634): (aquaporin 2) This gene encodes a water channel protein located in the kidney collecting tubule. It belongs to the MIP/aquaporin family, some members of which are clustered together on chromosome 12q13. Mutations in this gene have been linked to autosomal dominant and recessive forms of nephrogenic diabetes insipidus. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 12-49951193-G-A is Benign according to our data. Variant chr12-49951193-G-A is described in ClinVar as [Benign]. Clinvar id is 256243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49951193-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQP2 | NM_000486.6 | c.360+3G>A | splice_donor_region_variant, intron_variant | ENST00000199280.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQP2 | ENST00000199280.4 | c.360+3G>A | splice_donor_region_variant, intron_variant | 1 | NM_000486.6 | P1 | |||
AQP2 | ENST00000550862.1 | c.360+3G>A | splice_donor_region_variant, intron_variant | 5 | |||||
AQP2 | ENST00000551526.5 | c.360+3G>A | splice_donor_region_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.170 AC: 25929AN: 152132Hom.: 2539 Cov.: 33
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GnomAD3 exomes AF: 0.197 AC: 45710AN: 232494Hom.: 5294 AF XY: 0.206 AC XY: 26032AN XY: 126564
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GnomAD4 exome AF: 0.188 AC: 272814AN: 1448332Hom.: 28003 Cov.: 33 AF XY: 0.193 AC XY: 138660AN XY: 719146
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GnomAD4 genome ? AF: 0.170 AC: 25920AN: 152252Hom.: 2535 Cov.: 33 AF XY: 0.173 AC XY: 12841AN XY: 74412
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Diabetes insipidus, nephrogenic, autosomal Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 09, 2014 | - - |
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 10, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | This variant is associated with the following publications: (PMID: 27884173, 20814834) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Nephrogenic diabetes insipidus Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 09, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at