dbSNP rs2878771: AQP2:c.*3002G>C (chr12-49958610-G-C) – 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.*3002G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,284 control chromosomes in the GnomAD database, including 2,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2800 hom., cov: 33)

Exomes 𝑓: 0.20 ( 1 hom. )

Consequence

AQP2
NM_000486.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.67

Publications

18 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=-0.81).

BP6

Variant 12-49958610-G-C is Benign according to our data. Variant chr12-49958610-G-C is described in ClinVar as Benign. ClinVar VariationId is 309270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 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.*3002G>C	3_prime_UTR	Exon 4 of 4	NP_000477.1	P41181
AQP5-AS1	NR_110590.1		n.256+4057C>G	intron	N/A
AQP5-AS1	NR_110591.1		n.117+4057C>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AQP2	ENST00000199280.4	TSL:1 MANE Select	c.*3002G>C	3_prime_UTR	Exon 4 of 4	ENSP00000199280.3	P41181
AQP5-AS1	ENST00000550530.1	TSL:3	n.117+4057C>G	intron	N/A
AQP5-AS1	ENST00000552379.1	TSL:3	n.256+4057C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27883

AN:

152104

Hom.:

2801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

Cov.:

AF XY:

0.222

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.183

AC:

27884

AN:

152224

Hom.:

2800

Cov.:

AF XY:

0.185

AC XY:

13792

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.152

AC:

6316

AN:

41526

American (AMR)

AF:

0.141

AC:

2154

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

865

AN:

3470

East Asian (EAS)

AF:

0.364

AC:

1887

AN:

5180

South Asian (SAS)

AF:

0.320

AC:

1541

AN:

4816

European-Finnish (FIN)

AF:

0.179

AC:

1903

AN:

10608

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.184

AC:

12533

AN:

68008

Other (OTH)

AF:

0.211

AC:

446

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1185

2370

3554

4739

5924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.104

Hom.:

168

Bravo

AF:

0.175

Asia WGS

AF:

0.250

AC:

869

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Diabetes insipidus, nephrogenic, autosomal (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.52

PhyloP100

1.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over