12-5623852-A-T

Position:

• chr12-5623852-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ANO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2	c.1817-8555T>A		intron_variant		ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3	c.1832-8555T>A		intron_variant			NP_001265525.1
ANO2	NM_001278597.3	c.1820-8555T>A		intron_variant			NP_001265526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1	c.1817-8555T>A		intron_variant			NM_001364791.2	ENSP00000507275.1

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

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.805

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.715

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.668

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3782599; hg19: chr12-5733018;