Variant 12-5921308-C-T 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.266G>A(p.Arg89His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,613,916 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 2 hom. )

Consequence

ANO2
NM_001364791.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

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=0.0059717596).

BP6

Variant 12-5921308-C-T is Benign according to our data. Variant chr12-5921308-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642600.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2 linkuse as main transcript	c.266G>A	p.Arg89His	missense_variant	3/25	ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3 linkuse as main transcript	c.266G>A	p.Arg89His	missense_variant	3/27		NP_001265525.1	Q9NQ90-1F1T0L7
ANO2	NM_001278597.3 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	3/27		NP_001265526.1	Q9NQ90-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANO2	ENST00000682330.1 linkuse as main transcript	c.266G>A	p.Arg89His	missense_variant	3/25		NM_001364791.2	ENSP00000507275.1	A0A804HIY3
ANO2	ENST00000650848.1 linkuse as main transcript	c.266G>A	p.Arg89His	missense_variant	3/27			ENSP00000498903.1	Q9NQ90-1
ANO2	ENST00000327087.12 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	3/27	5			Q9NQ90-2
ANO2	ENST00000356134.9 linkuse as main transcript	c.254G>A	p.Arg85His	missense_variant	3/27	5		ENSP00000348453.5	Q9NQ90-2

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000967

AC:

241

AN:

249184

Hom.:

AF XY:

0.000806

AC XY:

109

AN XY:

135186

show subpopulations

Gnomad AFR exome

AF:

0.00853

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00746

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.000471

AC:

689

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

308

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00780

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.00869

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000980

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152222

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00775

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000949

Hom.:

Bravo

AF:

0.00274

ESP6500AA

AF:

0.00719

AC:

ESP6500EA

AF:

0.000474

AC:

ExAC

AF:

0.000892

AC:

108

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ANO2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;.;.

Eigen

Benign

-0.036

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

T;T;.

M_CAP

Benign

0.070

MetaRNN

Benign

0.0060

T;T;T

MetaSVM

Benign

-0.61

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.33

.;N;N

REVEL

Benign

0.17

Sift

Benign

0.23

.;T;T

Sift4G

Benign

0.15

T;T;T

Vest4

0.18

MVP

0.29

MPC

0.080

ClinPred

0.014

GERP RS

4.2

gMVP

0.24

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