Variant 12-5635329-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001364791.2(ANO2):c.1639A>G(p.Ile547Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,580,150 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 56 hom. )

Consequence

ANO2
NM_001364791.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.838

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006821841).

BP6

Variant 12-5635329-T-C is Benign according to our data. Variant chr12-5635329-T-C is described in ClinVar as [Benign]. Clinvar id is 770983.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2 linkuse as main transcript	c.1639A>G	p.Ile547Val	missense_variant	16/25	ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3 linkuse as main transcript	c.1654A>G	p.Ile552Val	missense_variant	18/27		NP_001265525.1	Q9NQ90-1F1T0L7
ANO2	NM_001278597.3 linkuse as main transcript	c.1642A>G	p.Ile548Val	missense_variant	18/27		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.1639A>G	p.Ile547Val	missense_variant	16/25		NM_001364791.2	ENSP00000507275.1		A0A804HIY3

Frequencies

GnomAD3 genomes

AF:

0.00636

AC:

967

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0247

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00929

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00750

AC:

1602

AN:

213594

Hom.:

AF XY:

0.00727

AC XY:

843

AN XY:

116014

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.000510

Gnomad ASJ exome

AF:

0.00146

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000866

Gnomad FIN exome

AF:

0.0233

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00812

GnomAD4 exome

AF:

0.00694

AC:

9916

AN:

1427942

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

4774

AN XY:

708978

show subpopulations

Gnomad4 AFR exome

AF:

0.000782

Gnomad4 AMR exome

AF:

0.000466

Gnomad4 ASJ exome

AF:

0.00120

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0227

Gnomad4 NFE exome

AF:

0.00758

Gnomad4 OTH exome

AF:

0.00549

GnomAD4 genome

AF:

0.00635

AC:

967

AN:

152208

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0247

Gnomad4 NFE

AF:

0.00929

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00712

Hom.:

Bravo

AF:

0.00386

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00255

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00850

AC:

1027

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

0.066

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.075

T;.;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.77

T;T;.;T

MetaRNN

Benign

0.0068

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.050

.;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.46

.;.;T;T

Sift4G

Benign

0.96

T;T;T;.

Vest4

0.42

MVP

0.088

MPC

0.061

ClinPred

0.019

GERP RS

5.0

gMVP

0.39

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

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