Variant 12-5575981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3BP4_StrongBP6_ModerateBS2

The NM_001364791.2(ANO2):c.2474C>T(p.Pro825Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,611,696 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 20 hom. )

Consequence

ANO2
NM_001364791.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.92

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 -9 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.03098774).

BP6

Variant 12-5575981-G-A is Benign according to our data. Variant chr12-5575981-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642598.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO2	NM_001364791.2 linkuse as main transcript	c.2474C>T	p.Pro825Leu	missense_variant	23/25	ENST00000682330.1	NP_001351720.1
ANO2	NM_001278596.3 linkuse as main transcript	c.2489C>T	p.Pro830Leu	missense_variant	25/27		NP_001265525.1	Q9NQ90-1F1T0L7
ANO2	NM_001278597.3 linkuse as main transcript	c.2477C>T	p.Pro826Leu	missense_variant	25/27		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.2474C>T	p.Pro825Leu	missense_variant	23/25		NM_001364791.2	ENSP00000507275.1	A0A804HIY3
ANO2	ENST00000650848.1 linkuse as main transcript	c.2489C>T	p.Pro830Leu	missense_variant	25/27			ENSP00000498903.1	Q9NQ90-1
ANO2	ENST00000327087.12 linkuse as main transcript	c.2477C>T	p.Pro826Leu	missense_variant	25/27	5			Q9NQ90-2
ANO2	ENST00000356134.9 linkuse as main transcript	c.2477C>T	p.Pro826Leu	missense_variant	25/27	5		ENSP00000348453.5	Q9NQ90-2

Frequencies

GnomAD3 genomes

AF:

0.00321

AC:

489

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00556

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00315

AC:

769

AN:

244432

Hom.:

AF XY:

0.00313

AC XY:

414

AN XY:

132360

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.00261

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000470

Gnomad FIN exome

AF:

0.00183

Gnomad NFE exome

AF:

0.00548

Gnomad OTH exome

AF:

0.00369

GnomAD4 exome

AF:

0.00464

AC:

6774

AN:

1459398

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

3347

AN XY:

725602

show subpopulations

Gnomad4 AFR exome

AF:

0.000718

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000350

Gnomad4 FIN exome

AF:

0.00219

Gnomad4 NFE exome

AF:

0.00560

Gnomad4 OTH exome

AF:

0.00370

GnomAD4 genome

AF:

0.00321

AC:

489

AN:

152298

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00556

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00457

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000509

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00318

AC:

384

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

Jan 01, 2023

ANO2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.94

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;D;.

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Uncertain

0.36

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-9.1

.;.;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.89

MVP

0.81

MPC

0.38

ClinPred

0.17

GERP RS

5.1

gMVP

0.85

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