dbSNP rs467323: AQP2:c.*374C>G (chr12-49955982-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000486.6(AQP2):c.*374C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AQP2
NM_000486.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.521

Publications

17 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:

ENSG00000257378 (HGNC:):

ENSG00000257378 links:

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

AQP5-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AQP2	NM_000486.6 link	c.*374C>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000199280.4	NP_000477.1	P41181
AQP5-AS1	NR_110590.1 link	n.257-1634G>C	intron_variant	Intron 1 of 2
AQP5-AS1	NR_110591.1 link	n.118-3894G>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.*374C>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_000486.6	ENSP00000199280.3		P41181

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

273110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

142402

African (AFR)

AF:

0.00

AC:

AN:

8526

American (AMR)

AF:

0.00

AC:

AN:

11928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8300

East Asian (EAS)

AF:

0.00

AC:

AN:

16504

South Asian (SAS)

AF:

0.00

AC:

AN:

34108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

160666

Other (OTH)

AF:

0.00

AC:

AN:

16054

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

38897

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.8

(source)

DANN

Benign

0.57

PhyloP100

0.52

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over