GeneBe

rs104894339

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_000486.6(AQP2):ā€‹c.785C>Gā€‹(p.Pro262Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,433,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

AQP2
NM_000486.6 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.86
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1
In a chain Aquaporin-2 (size 270) in uniprot entity AQP2_HUMAN there are 17 pathogenic changes around while only 2 benign (89%) in NM_000486.6
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36839992).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AQP2NM_000486.6 linkc.785C>G p.Pro262Arg missense_variant Exon 4 of 4 ENST00000199280.4 NP_000477.1 P41181
AQP5-AS1NR_110590.1 linkn.257-1229G>C intron_variant Intron 1 of 2
AQP5-AS1NR_110591.1 linkn.118-3489G>C intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AQP2ENST00000199280.4 linkc.785C>G p.Pro262Arg missense_variant Exon 4 of 4 1 NM_000486.6 ENSP00000199280.3 P41181

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000499
AC:
1
AN:
200378
Hom.:
0
AF XY:
0.00000904
AC XY:
1
AN XY:
110614
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000691
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1433862
Hom.:
0
Cov.:
66
AF XY:
0.00000140
AC XY:
1
AN XY:
712128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000225
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.37
T
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.27
Sift
Uncertain
0.023
D
Sift4G
Uncertain
0.052
T
Polyphen
0.97
D
Vest4
0.31
MutPred
0.37
Gain of MoRF binding (P = 0.0081);
MVP
0.94
MPC
1.2
ClinPred
0.72
D
GERP RS
4.7
Varity_R
0.16
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs104894339; hg19: chr12-50349360; API