12-5642176-C-T

Variant names:

• chr12-5642176-C-T
• rs2110166
• NM_001364791.2:c.1620+5551G>A

Variant summary

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

The NM_001364791.2(ANO2):​c.1620+5551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,228 control chromosomes in the GnomAD database, including 371 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 0.059 (371 hom., cov: 32)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 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.1620+5551G>A		intron	N/A	NP_001351720.1	A0A804HIY3
	ANO2	NM_001278596.3		c.1635+5551G>A		intron	N/A	NP_001265525.1	Q9NQ90-1
	ANO2	NM_001278597.3		c.1623+5551G>A		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.1620+5551G>A		intron	N/A	ENSP00000507275.1	A0A804HIY3
	ANO2	ENST00000650848.1		c.1635+5551G>A		intron	N/A	ENSP00000498903.1	Q9NQ90-1
	ANO2	ENST00000356134.9	TSL:5	c.1623+5551G>A		intron	N/A	ENSP00000348453.5	Q9NQ90-2

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8888 AN: 152110 Hom.: 371 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0696

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0585 AC: 8909 AN: 152228 Hom.: 371 Cov.: 32 AF XY: 0.0616 AC XY: 4582 AN XY: 74430

African (AFR) AF: 0.101 AC: 4188 AN: 41498

American (AMR) AF: 0.0697 AC: 1067 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.118 AC: 613 AN: 5188

South Asian (SAS) AF: 0.0563 AC: 271 AN: 4816

European-Finnish (FIN) AF: 0.0382 AC: 405 AN: 10606

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0303 AC: 2060 AN: 68032

Other (OTH) AF: 0.0578 AC: 122 AN: 2110

Alfa AF: 0.0460 Hom.: 343

Bravo AF: 0.0635

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.33
PhyloP100		-0.010
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: rs2110166; hg19: chr12-5751342;