rs10492181

Variant names:

• chr12-5640197-A-G
• rs10492181
• NM_001364791.2:c.1621-4850T>C

Variant summary

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

The NM_001278596.3(ANO2):​c.1636-4850T>C 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 152,210 control chromosomes in the GnomAD database, including 1,566 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 0.13 (1566 hom., cov: 32)
• Consequence: ANO2 NM_001278596.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278596.3. 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
	ANO2	NM_001364791.2	MANE Select	c.1621-4850T>C		intron	N/A	NP_001351720.1
	ANO2	NM_001278596.3		c.1636-4850T>C		intron	N/A	NP_001265525.1
	ANO2	NM_001278597.3		c.1624-4850T>C		intron	N/A	NP_001265526.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANO2	ENST00000682330.1	MANE Select	c.1621-4850T>C		intron	N/A	ENSP00000507275.1
	ANO2	ENST00000650848.1		c.1636-4850T>C		intron	N/A	ENSP00000498903.1
	ANO2	ENST00000356134.9	TSL:5	c.1624-4850T>C		intron	N/A	ENSP00000348453.5

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19204 AN: 152092 Hom.: 1562 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.126 AC: 19219 AN: 152210 Hom.: 1566 Cov.: 32 AF XY: 0.128 AC XY: 9509 AN XY: 74416

African (AFR) AF: 0.0321 AC: 1334 AN: 41564

American (AMR) AF: 0.185 AC: 2837 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.0302 AC: 156 AN: 5170

South Asian (SAS) AF: 0.202 AC: 974 AN: 4814

European-Finnish (FIN) AF: 0.138 AC: 1464 AN: 10592

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.169 AC: 11477 AN: 67982

Other (OTH) AF: 0.132 AC: 280 AN: 2114

Alfa AF: 0.159 Hom.: 3924

Bravo AF: 0.123

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.56
PhyloP100		2.6
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: rs10492181; hg19: chr12-5749363;