rs199422215
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_000486.6(AQP2):c.647C>T(p.Ser216Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S216P) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 34)
Consequence
AQP2
NM_000486.6 missense
NM_000486.6 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 4.13
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]
AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a chain Aquaporin-2 (size 270) in uniprot entity AQP2_HUMAN there are 44 pathogenic changes around while only 9 benign (83%) in NM_000486.6
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr12-49955438-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 17829.Status of the report is no_assertion_criteria_provided, 0 stars.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.991
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AQP2 | NM_000486.6 | c.647C>T | p.Ser216Phe | missense_variant | 4/4 | ENST00000199280.4 | |
AQP5-AS1 | NR_110591.1 | n.118-3351G>A | intron_variant, non_coding_transcript_variant | ||||
AQP5-AS1 | NR_110590.1 | n.257-1091G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AQP2 | ENST00000199280.4 | c.647C>T | p.Ser216Phe | missense_variant | 4/4 | 1 | NM_000486.6 | P1 | |
AQP5-AS1 | ENST00000550530.1 | n.118-3351G>A | intron_variant, non_coding_transcript_variant | 3 | |||||
ENST00000552806.1 | n.541+146G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Cov.: 64
GnomAD4 exome
Cov.:
64
GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of helix (P = 0.2294);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at