Variant 12-5732874-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001278596.3(ANO2):c.1441C>T(p.Arg481Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,970 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 83 hom. )

Consequence

ANO2
NM_001278596.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.89

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055063367).

BP6

Variant 12-5732874-G-A is Benign according to our data. Variant chr12-5732874-G-A is described in ClinVar as [Benign]. Clinvar id is 782873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00236 (360/152302) while in subpopulation SAS AF= 0.029 (140/4828). AF 95% confidence interval is 0.0251. There are 6 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2 linkuse as main transcript	c.1435-244C>T		intron_variant		ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3 linkuse as main transcript	c.1441C>T	p.Arg481Cys	missense_variant	15/27		NP_001265525.1	Q9NQ90-1F1T0L7
ANO2	NM_001278597.3 linkuse as main transcript	c.1429C>T	p.Arg477Cys	missense_variant	15/27		NP_001265526.1	Q9NQ90-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO2	ENST00000682330.1 linkuse as main transcript	c.1435-244C>T		intron_variant			NM_001364791.2	ENSP00000507275.1		A0A804HIY3

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

361

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0245

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00565

AC:

1407

AN:

249208

Hom.:

AF XY:

0.00667

AC XY:

902

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.000969

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.0257

Gnomad SAS exome

AF:

0.0256

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000805

Gnomad OTH exome

AF:

0.00380

GnomAD4 exome

AF:

0.00285

AC:

4160

AN:

1461668

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

2570

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.000738

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0262

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.000423

Gnomad4 OTH exome

AF:

0.00550

GnomAD4 genome

AF:

0.00236

AC:

360

AN:

152302

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

232

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0243

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000742

AC:

ESP6500EA

AF:

0.00107

AC:

ExAC

AF:

0.00611

AC:

739

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Pathogenic

1.0

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.52

T;.

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.54

.;N

REVEL

Benign

0.095

Sift

Benign

0.080

.;T

Sift4G

Uncertain

0.045

D;D

Vest4

0.59

MVP

0.39

MPC

0.26

ClinPred

0.036

GERP RS

3.8

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over