Genetic Variant AQP2:c.607-39C>G (chr12-49955360-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000486.6(AQP2):c.607-39C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,598,764 control chromosomes in the GnomAD database, including 495,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 40090 hom., cov: 34)

Exomes 𝑓: 0.79 ( 455707 hom. )

Consequence

AQP2
NM_000486.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.05

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 12-49955360-C-G is Benign according to our data. Variant chr12-49955360-C-G is described in ClinVar as [Benign]. Clinvar id is 1180579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AQP2	NM_000486.6 link	c.607-39C>G	intron_variant	Intron 3 of 3	ENST00000199280.4	NP_000477.1	P41181
AQP5-AS1	NR_110590.1 link	n.257-1012G>C	intron_variant	Intron 1 of 2
AQP5-AS1	NR_110591.1 link	n.118-3272G>C	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4 link	c.607-39C>G		intron_variant	Intron 3 of 3	1	NM_000486.6	ENSP00000199280.3		P41181

Frequencies

GnomAD3 genomes

AF:

0.710

AC:

107974

AN:

152118

Hom.:

40053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.844

Gnomad MID

AF:

0.685

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.717

GnomAD3 exomes

AF:

0.772

AC:

174849

AN:

226392

Hom.:

68626

AF XY:

0.769

AC XY:

96235

AN XY:

125080

show subpopulations

Gnomad AFR exome

AF:

0.473

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.737

Gnomad EAS exome

AF:

0.630

Gnomad SAS exome

AF:

0.703

Gnomad FIN exome

AF:

0.845

Gnomad NFE exome

AF:

0.808

Gnomad OTH exome

AF:

0.776

GnomAD4 exome

AF:

0.791

AC:

1143716

AN:

1446528

Hom.:

455707

Cov.:

AF XY:

0.788

AC XY:

566100

AN XY:

718118

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.867

Gnomad4 ASJ exome

AF:

0.733

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.699

Gnomad4 FIN exome

AF:

0.845

Gnomad4 NFE exome

AF:

0.811

Gnomad4 OTH exome

AF:

0.759

GnomAD4 genome

AF:

0.710

AC:

108064

AN:

152236

Hom.:

40090

Cov.:

AF XY:

0.712

AC XY:

53043

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.483

Gnomad4 AMR

AF:

0.819

Gnomad4 ASJ

AF:

0.730

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.693

Gnomad4 FIN

AF:

0.844

Gnomad4 NFE

AF:

0.807

Gnomad4 OTH

AF:

0.721

Alfa

AF:

0.754

Hom.:

8143

Bravo

AF:

0.701

Asia WGS

AF:

0.736

AC:

2560

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 10, 2018

GeneDx

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:1

Jul 10, 2021

Genome-Nilou Lab

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

0.61

DANN

Benign

0.069

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over