Variant 12-5832446-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001364791.2(ANO2):c.785+6T>A variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00523 in 1,613,670 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 40 hom. )

Consequence

ANO2
NM_001364791.2 splice_donor_region, intron

Scores

Splicing: ADA: 0.9971

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.81

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 12-5832446-A-T is Benign according to our data. Variant chr12-5832446-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642599.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANO2	NM_001364791.2 linkuse as main transcript	c.785+6T>A	splice_donor_region_variant, intron_variant	ENST00000682330.1
ANO2	NM_001278596.3 linkuse as main transcript	c.788+6T>A	splice_donor_region_variant, intron_variant
ANO2	NM_001278597.3 linkuse as main transcript	c.776+6T>A	splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ANO2	ENST00000682330.1 linkuse as main transcript	c.785+6T>A	splice_donor_region_variant, intron_variant		NM_001364791.2	P4
ANO2	ENST00000356134.9 linkuse as main transcript	c.776+6T>A	splice_donor_region_variant, intron_variant	5			Q9NQ90-2
ANO2	ENST00000650848.1 linkuse as main transcript	c.788+6T>A	splice_donor_region_variant, intron_variant			A2	Q9NQ90-1
ANO2	ENST00000544988.1 linkuse as main transcript	n.453+6T>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00470

AC:

715

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000629

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00632

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00554

AC:

1380

AN:

249050

Hom.:

AF XY:

0.00556

AC XY:

751

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00420

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.0139

Gnomad NFE exome

AF:

0.00719

Gnomad OTH exome

AF:

0.00629

GnomAD4 exome

AF:

0.00528

AC:

7720

AN:

1461578

Hom.:

Cov.:

AF XY:

0.00516

AC XY:

3749

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00458

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00457

GnomAD4 genome

AF:

0.00470

AC:

715

AN:

152092

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

362

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.00631

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00509

Hom.:

Bravo

AF:

0.00403

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00562

EpiControl

AF:

0.00753

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

Mar 01, 2023

ANO2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Uncertain

Dann

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Benign

0.72

SpliceAI score (max)

0.18

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