chr12-5598206-T-G

Variant names:

• chr12-5598206-T-G
• rs728342
• NM_001364791.2:c.2233+1278A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364791.2(ANO2):​c.2233+1278A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,040 control chromosomes in the GnomAD database, including 6,730 homozygotes. 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: 𝑓 0.29 (6730 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 2 publications found

Genes affected

ANO2 (HGNC:1183): (anoctamin 2) ANO2 belongs to a family of calcium-activated chloride channels (CaCCs) (reviewed by Hartzell et al., 2009 [PubMed 19015192]).[supplied by OMIM, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364791.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	NM_001364791.2	MANE Select	c.2233+1278A>C		intron	N/A	NP_001351720.1	A0A804HIY3
	ANO2	NM_001278596.3		c.2248+1278A>C		intron	N/A	NP_001265525.1	Q9NQ90-1
	ANO2	NM_001278597.3		c.2236+1278A>C		intron	N/A	NP_001265526.1	Q9NQ90-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	ENST00000682330.1	MANE Select	c.2233+1278A>C		intron	N/A	ENSP00000507275.1	A0A804HIY3
	ANO2	ENST00000650848.1		c.2248+1278A>C		intron	N/A	ENSP00000498903.1	Q9NQ90-1
	ANO2	ENST00000356134.9	TSL:5	c.2236+1278A>C		intron	N/A	ENSP00000348453.5	Q9NQ90-2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44672 AN: 151922 Hom.: 6723 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44701 AN: 152040 Hom.: 6730 Cov.: 32 AF XY: 0.290 AC XY: 21558 AN XY: 74304

African (AFR) AF: 0.229 AC: 9495 AN: 41484

American (AMR) AF: 0.318 AC: 4858 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3470

East Asian (EAS) AF: 0.193 AC: 997 AN: 5164

South Asian (SAS) AF: 0.264 AC: 1268 AN: 4800

European-Finnish (FIN) AF: 0.288 AC: 3046 AN: 10572

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22792 AN: 67956

Other (OTH) AF: 0.302 AC: 636 AN: 2106

Alfa AF: 0.301 Hom.: 4105

Bravo AF: 0.295

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.52
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: rs728342; hg19: chr12-5707372;