chr12-49955982-C-G

Variant names:

• chr12-49955982-C-G
• rs467323
• NM_000486.6:c.*374C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 17 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]

ENSG00000257378 (HGNC:):

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

ACMG classification

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).

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.*374C>G		3_prime_UTR	Exon 4 of 4	NP_000477.1
	AQP5-AS1	NR_110590.1		n.257-1634G>C		intron	N/A
	AQP5-AS1	NR_110591.1		n.118-3894G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AQP2	ENST00000199280.4	TSL:1 MANE Select	c.*374C>G		3_prime_UTR	Exon 4 of 4	ENSP00000199280.3
	ENSG00000257378	ENST00000552806.1	TSL:5	n.144G>C		non_coding_transcript_exon	Exon 1 of 2
	AQP5-AS1	ENST00000550530.1	TSL:3	n.118-3894G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 273110 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 142402

African (AFR) AF: 0.00 AC: 0 AN: 8526

American (AMR) AF: 0.00 AC: 0 AN: 11928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8300

East Asian (EAS) AF: 0.00 AC: 0 AN: 16504

South Asian (SAS) AF: 0.00 AC: 0 AN: 34108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 160666

Other (OTH) AF: 0.00 AC: 0 AN: 16054

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 38897

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
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

Other links and lift over

dbSNP: rs467323; hg19: chr12-50349765;