12-5623852-A-T

Variant names:

• chr12-5623852-A-T
• rs3782599
• NM_001364791.2:c.1817-8555T>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.1817-8555T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,948 control chromosomes in the GnomAD database, including 33,532 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 0.66 (33532 hom., cov: 33)
• Consequence: ANO2 NM_001364791.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 1 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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO2	NM_001364791.2	c.1817-8555T>A		intron_variant	Intron 16 of 24	ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3	c.1832-8555T>A		intron_variant	Intron 18 of 26		NP_001265525.1
ANO2	NM_001278597.3	c.1820-8555T>A		intron_variant	Intron 18 of 26		NP_001265526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1	c.1817-8555T>A		intron_variant	Intron 16 of 24		NM_001364791.2	ENSP00000507275.1
ANO2	ENST00000650848.1	c.1832-8555T>A		intron_variant	Intron 18 of 26			ENSP00000498903.1
ANO2	ENST00000356134.9	c.1820-8555T>A		intron_variant	Intron 18 of 26	5		ENSP00000348453.5
ANO2	ENST00000545860.1	c.497-8555T>A		intron_variant	Intron 5 of 5	3		ENSP00000443813.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100530 AN: 151828 Hom.: 33506 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.662 AC: 100597 AN: 151948 Hom.: 33532 Cov.: 33 AF XY: 0.668 AC XY: 49615 AN XY: 74304

African (AFR) AF: 0.581 AC: 24072 AN: 41432

American (AMR) AF: 0.662 AC: 10118 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2389 AN: 3468

East Asian (EAS) AF: 0.805 AC: 4156 AN: 5160

South Asian (SAS) AF: 0.734 AC: 3527 AN: 4808

European-Finnish (FIN) AF: 0.715 AC: 7541 AN: 10544

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46526 AN: 67936

Other (OTH) AF: 0.668 AC: 1410 AN: 2110

Alfa AF: 0.577 Hom.: 1695

Bravo AF: 0.652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.8
DANN	Benign	0.67
PhyloP100		-0.083
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: rs3782599; hg19: chr12-5733018;