dbSNP rs461872: AQP2:c.360+233G>A (chr12-49951423-G-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.360+233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 611,596 control chromosomes in the GnomAD database, including 66,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13797 hom., cov: 32)

Exomes 𝑓: 0.46 ( 52306 hom. )

Consequence

AQP2
NM_000486.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.52

Publications

12 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-49951423-G-A is Benign according to our data. Variant chr12-49951423-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AQP2	NM_000486.6 link	c.360+233G>A		intron_variant	Intron 1 of 3	ENST00000199280.4	NP_000477.1
AQP5-AS1	NR_110591.1 link	n.*89C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
AQP2	ENST00000199280.4 link	c.360+233G>A	intron_variant	Intron 1 of 3	1	NM_000486.6	ENSP00000199280.3
AQP2	ENST00000550862.1 link	c.360+233G>A	intron_variant	Intron 1 of 2	5		ENSP00000450022.1
AQP2	ENST00000551526.5 link	n.360+233G>A	intron_variant	Intron 1 of 5	5		ENSP00000447148.1
AQP5-AS1	ENST00000550530.1 link	n.*89C>T	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60686

AN:

151988

Hom.:

13789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.353

Gnomad EAS

AF:

0.224

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.555

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.418

GnomAD4 exome

AF:

0.460

AC:

211279

AN:

459490

Hom.:

52306

AF XY:

0.454

AC XY:

106397

AN XY:

234362

show subpopulations

African (AFR)

AF:

0.186

AC:

2432

AN:

13082

American (AMR)

AF:

0.403

AC:

6826

AN:

16954

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

4550

AN:

12966

East Asian (EAS)

AF:

0.206

AC:

6223

AN:

30248

South Asian (SAS)

AF:

0.242

AC:

7481

AN:

30876

European-Finnish (FIN)

AF:

0.572

AC:

15557

AN:

27216

Middle Eastern (MID)

AF:

0.385

AC:

743

AN:

1928

European-Non Finnish (NFE)

AF:

0.520

AC:

156191

AN:

300386

Other (OTH)

AF:

0.436

AC:

11276

AN:

25834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

5221

10443

15664

20886

26107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1730

3460

5190

6920

8650

<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:

0.399

AC:

60706

AN:

152106

Hom.:

13797

Cov.:

AF XY:

0.397

AC XY:

29513

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.198

AC:

8203

AN:

41490

American (AMR)

AF:

0.405

AC:

6199

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.353

AC:

1224

AN:

3470

East Asian (EAS)

AF:

0.223

AC:

1152

AN:

5174

South Asian (SAS)

AF:

0.228

AC:

1102

AN:

4826

European-Finnish (FIN)

AF:

0.555

AC:

5867

AN:

10566

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.522

AC:

35515

AN:

67972

Other (OTH)

AF:

0.414

AC:

871

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1747

3494

5240

6987

8734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.478

Hom.:

29480

Bravo

AF:

0.382

Asia WGS

AF:

0.209

AC:

727

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.37

(source)

DANN

Benign

0.45

PhyloP100

-1.5

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