rs3782322

Positions:

• chr12-49951517-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000486.6(AQP2):​c.360+327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 349,918 control chromosomes in the GnomAD database, including 4,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2055 hom., cov: 33)
  • Exomes 𝑓: 0.11 (1968 hom.)
• Consequence: AQP2 NM_000486.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.460

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]

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-49951517-G-A is Benign according to our data. Variant chr12-49951517-G-A is described in ClinVar as [Benign]. Clinvar id is 1221038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AQP2	NM_000486.6	c.360+327G>A		intron_variant		ENST00000199280.4	NP_000477.1
AQP5-AS1	NR_110591.1	n.440C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AQP2	ENST00000199280.4	c.360+327G>A		intron_variant		1	NM_000486.6	ENSP00000199280	P1
AQP5-AS1	ENST00000550530.1	n.440C>T		non_coding_transcript_exon_variant	3/3	3
AQP2	ENST00000550862.1	c.360+327G>A		intron_variant		5		ENSP00000450022
AQP2	ENST00000551526.5	c.360+327G>A		intron_variant, NMD_transcript_variant		5		ENSP00000447148

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21339 AN: 152070 Hom.: 2042 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.114 AC: 22574 AN: 197730 Hom.: 1968 Cov.: 0 AF XY: 0.116 AC XY: 11670 AN XY: 100214

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.0811

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0740

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.140 AC: 21379 AN: 152188 Hom.: 2055 Cov.: 33 AF XY: 0.143 AC XY: 10659 AN XY: 74412

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.0792

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.0721

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.128

Alfa AF: 0.104 Hom.: 148

Bravo AF: 0.151

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs3782322; hg19: chr12-50345300;