11-22221183-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_213599.3(ANO5):c.267T>C(p.Asp89Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 1,610,396 control chromosomes in the GnomAD database, including 518,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.83 ( 52348 hom., cov: 32)

Exomes 𝑓: 0.80 ( 466471 hom. )

Consequence

ANO5
NM_213599.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:19O:2

Conservation

PhyloP100: -0.700

Publications

27 publications found

Variant links:

Genes affected

ANO5 (HGNC:27337): (anoctamin 5) This gene encodes a member of the anoctamin family of transmembrane proteins. The encoded protein is likely a calcium activated chloride channel. Mutations in this gene have been associated with gnathodiaphyseal dysplasia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

ANO5 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
gnathodiaphyseal dysplasia
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive limb-girdle muscular dystrophy type 2L
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
Miyoshi muscular dystrophy 3
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ANO5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-22221183-T-C is Benign according to our data. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22221183-T-C is described in CliVar as Benign. Clinvar id is 96681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3 link	c.267T>C	p.Asp89Asp	synonymous_variant	Exon 5 of 22	ENST00000324559.9	NP_998764.1	Q75V66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9 link	c.267T>C	p.Asp89Asp	synonymous_variant	Exon 5 of 22	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.826

AC:

125391

AN:

151818

Hom.:

52294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.930

Gnomad AMI

AF:

0.877

Gnomad AMR

AF:

0.719

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.803

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.810

GnomAD2 exomes

AF:

0.766

AC:

191380

AN:

249920

AF XY:

0.772

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.601

Gnomad ASJ exome

AF:

0.744

Gnomad EAS exome

AF:

0.554

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.807

Gnomad OTH exome

AF:

0.780

GnomAD4 exome

AF:

0.797

AC:

1162290

AN:

1458460

Hom.:

466471

Cov.:

AF XY:

0.797

AC XY:

578577

AN XY:

725672

show subpopulations

African (AFR)

AF:

0.936

AC:

31206

AN:

33352

American (AMR)

AF:

0.615

AC:

27396

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

19600

AN:

26052

East Asian (EAS)

AF:

0.527

AC:

20827

AN:

39518

South Asian (SAS)

AF:

0.803

AC:

69175

AN:

86154

European-Finnish (FIN)

AF:

0.812

AC:

43266

AN:

53288

Middle Eastern (MID)

AF:

0.818

AC:

4696

AN:

5744

European-Non Finnish (NFE)

AF:

0.810

AC:

898327

AN:

1109632

Other (OTH)

AF:

0.794

AC:

47797

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11035

22071

33106

44142

55177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20758

41516

62274

83032

103790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.826

AC:

125507

AN:

151936

Hom.:

52348

Cov.:

AF XY:

0.823

AC XY:

61097

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.930

AC:

38624

AN:

41520

American (AMR)

AF:

0.719

AC:

10951

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.753

AC:

2612

AN:

3470

East Asian (EAS)

AF:

0.559

AC:

2877

AN:

5146

South Asian (SAS)

AF:

0.806

AC:

3885

AN:

4820

European-Finnish (FIN)

AF:

0.820

AC:

8672

AN:

10580

Middle Eastern (MID)

AF:

0.805

AC:

235

AN:

292

European-Non Finnish (NFE)

AF:

0.813

AC:

55138

AN:

67852

Other (OTH)

AF:

0.812

AC:

1713

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1088

2177

3265

4354

5442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.806

Hom.:

68620

Bravo

AF:

0.815

Asia WGS

AF:

0.724

AC:

2518

AN:

3474

EpiCase

AF:

0.800

EpiControl

AF:

0.800

ClinVar

Significance: Benign

Submissions summary: Benign:19Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:10

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Asp89Asp in exon 5 of ANO5: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 20.0% (1723/8598) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs4312063). -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

ANO5 @LOVD

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Jul 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Miyoshi muscular dystrophy 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ANO5-Related Muscle Diseases

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gnathodiaphyseal dysplasia

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Miyoshi myopathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ANO5-related disorder

Other:1

GenomeConnect - Invitae Patient Insights Network

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 11-11-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.59

(source)

DANN

Benign

0.36

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over