dbSNP rs371777: AQP2:c.607-59C>A (chr12-49955340-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000486.6(AQP2):c.607-59C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,555,686 control chromosomes in the GnomAD database, including 294,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26327 hom., cov: 34)

Exomes 𝑓: 0.62 ( 267900 hom. )

Consequence

AQP2
NM_000486.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.935

Publications

7 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:

ENSG00000257378 (HGNC:):

ENSG00000257378 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-49955340-C-A is Benign according to our data. Variant chr12-49955340-C-A is described in ClinVar as Benign. ClinVar VariationId is 1180565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000486.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP2	NM_000486.6	MANE Select	c.607-59C>A	intron	N/A	NP_000477.1	P41181
AQP5-AS1	NR_110590.1		n.257-992G>T	intron	N/A
AQP5-AS1	NR_110591.1		n.118-3252G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP2	ENST00000199280.4	TSL:1 MANE Select	c.607-59C>A	intron	N/A	ENSP00000199280.3	P41181
AQP5-AS1	ENST00000550530.1	TSL:3	n.118-3252G>T	intron	N/A
AQP2	ENST00000551526.5	TSL:5	n.607-59C>A	intron	N/A	ENSP00000447148.1	F8W0S2

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88156

AN:

152036

Hom.:

26295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.688

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.578

GnomAD4 exome

AF:

0.616

AC:

864575

AN:

1403532

Hom.:

267900

AF XY:

0.617

AC XY:

429159

AN XY:

695922

show subpopulations

African (AFR)

AF:

0.436

AC:

13872

AN:

31804

American (AMR)

AF:

0.772

AC:

32181

AN:

41672

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

12335

AN:

24596

East Asian (EAS)

AF:

0.606

AC:

23147

AN:

38198

South Asian (SAS)

AF:

0.637

AC:

52529

AN:

82466

European-Finnish (FIN)

AF:

0.696

AC:

34924

AN:

50148

Middle Eastern (MID)

AF:

0.518

AC:

2418

AN:

4672

European-Non Finnish (NFE)

AF:

0.615

AC:

658945

AN:

1072130

Other (OTH)

AF:

0.592

AC:

34224

AN:

57846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

17400

34801

52201

69602

87002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17798

35596

53394

71192

88990

<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:

0.580

AC:

88233

AN:

152154

Hom.:

26327

Cov.:

AF XY:

0.585

AC XY:

43498

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.443

AC:

18373

AN:

41518

American (AMR)

AF:

0.689

AC:

10529

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.497

AC:

1724

AN:

3472

East Asian (EAS)

AF:

0.621

AC:

3200

AN:

5154

South Asian (SAS)

AF:

0.626

AC:

3020

AN:

4828

European-Finnish (FIN)

AF:

0.697

AC:

7382

AN:

10592

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42096

AN:

67986

Other (OTH)

AF:

0.579

AC:

1223

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1872

3744

5615

7487

9359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.527

Hom.:

1774

Bravo

AF:

0.575

Asia WGS

AF:

0.640

AC:

2226

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Diabetes insipidus, nephrogenic, autosomal (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.0

(source)

DANN

Benign

0.79

PhyloP100

-0.94

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over