rs426496

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000486.6(AQP2):c.501T>C(p.Ser167Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,608,946 control chromosomes in the GnomAD database, including 498,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 40074 hom., cov: 31)

Exomes 𝑓: 0.79 ( 458430 hom. )

Consequence

AQP2
NM_000486.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.37

Publications

22 publications found

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]

AQP2 links:

AQP5-AS1 (HGNC:55474): (AQP5 and AQP2 antisense RNA 2)

AQP5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-49954295-T-C is Benign according to our data. Variant chr12-49954295-T-C is described in ClinVar as Benign. ClinVar VariationId is 504917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
AQP2	NM_000486.6 link	c.501T>C	p.Ser167Ser	synonymous_variant	Exon 2 of 4	ENST00000199280.4	NP_000477.1
AQP5-AS1	NR_110590.1 link	n.310A>G		non_coding_transcript_exon_variant	Exon 2 of 3
AQP5-AS1	NR_110591.1 link	n.118-2207A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4 link	c.501T>C	p.Ser167Ser	synonymous_variant	Exon 2 of 4	1	NM_000486.6	ENSP00000199280.3

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107887

AN:

151888

Hom.:

40036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.718

GnomAD2 exomes

AF:

0.766

AC:

188673

AN:

246408

AF XY:

0.765

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.875

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.790

AC:

1151098

AN:

1456940

Hom.:

458430

Cov.:

AF XY:

0.788

AC XY:

570946

AN XY:

724942

show subpopulations

African (AFR)

AF:

0.470

AC:

15734

AN:

33472

American (AMR)

AF:

0.866

AC:

38684

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

19117

AN:

26126

East Asian (EAS)

AF:

0.633

AC:

25108

AN:

39696

South Asian (SAS)

AF:

0.698

AC:

60206

AN:

86240

European-Finnish (FIN)

AF:

0.844

AC:

41240

AN:

48872

Middle Eastern (MID)

AF:

0.676

AC:

3897

AN:

5766

European-Non Finnish (NFE)

AF:

0.811

AC:

901374

AN:

1111754

Other (OTH)

AF:

0.758

AC:

45738

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

14954

29909

44863

59818

74772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20758

41516

62274

83032

103790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.710

AC:

107978

AN:

152006

Hom.:

40074

Cov.:

AF XY:

0.713

AC XY:

52979

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.484

AC:

20036

AN:

41426

American (AMR)

AF:

0.819

AC:

12525

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.730

AC:

2533

AN:

3472

East Asian (EAS)

AF:

0.639

AC:

3287

AN:

5142

South Asian (SAS)

AF:

0.694

AC:

3341

AN:

4816

European-Finnish (FIN)

AF:

0.844

AC:

8934

AN:

10586

Middle Eastern (MID)

AF:

0.680

AC:

200

AN:

294

European-Non Finnish (NFE)

AF:

0.808

AC:

54895

AN:

67960

Other (OTH)

AF:

0.722

AC:

1521

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1466

2933

4399

5866

7332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.771

Hom.:

21725

Bravo

AF:

0.702

Asia WGS

AF:

0.737

AC:

2563

AN:

3478

EpiCase

AF:

0.801

EpiControl

AF:

0.795

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ser167Ser in exon 2 of AQP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 88.04% (10065/11432) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs426496). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Diabetes insipidus, nephrogenic, autosomal

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 09, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrogenic diabetes insipidus

Benign:1

Nov 18, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.35

(source)

DANN

Benign

0.55

PhyloP100

-4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over