chr12-49951517-G-A

Variant names:

• chr12-49951517-G-A
• rs3782322
• NM_000486.6:c.360+327G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP2	NM_000486.6	MANE Select	c.360+327G>A		intron	N/A	NP_000477.1
	AQP5-AS1	NR_110591.1		n.440C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP2	ENST00000199280.4	TSL:1 MANE Select	c.360+327G>A		intron	N/A	ENSP00000199280.3
	AQP5-AS1	ENST00000550530.1	TSL:3	n.440C>T		non_coding_transcript_exon	Exon 3 of 3
	AQP2	ENST00000550862.1	TSL:5	c.360+327G>A		intron	N/A	ENSP00000450022.1

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

African (AFR) AF: 0.206 AC: 1540 AN: 7458

American (AMR) AF: 0.252 AC: 2123 AN: 8418

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 588 AN: 7246

East Asian (EAS) AF: 0.255 AC: 4170 AN: 16330

South Asian (SAS) AF: 0.319 AC: 2593 AN: 8134

European-Finnish (FIN) AF: 0.0696 AC: 870 AN: 12494

Middle Eastern (MID) AF: 0.100 AC: 99 AN: 986

European-Non Finnish (NFE) AF: 0.0740 AC: 9178 AN: 123970

Other (OTH) AF: 0.111 AC: 1413 AN: 12694

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

African (AFR) AF: 0.203 AC: 8435 AN: 41514

American (AMR) AF: 0.240 AC: 3675 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 275 AN: 3472

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5174

South Asian (SAS) AF: 0.321 AC: 1546 AN: 4812

European-Finnish (FIN) AF: 0.0721 AC: 764 AN: 10602

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0756 AC: 5144 AN: 68002

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.108 Hom.: 168

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3782322; hg19: chr12-50345300;