11-22274548-CTTTTT-CTTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_213599.3(ANO5):c.2236-10delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,076,456 control chromosomes in the GnomAD database, including 2,188 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 227 hom., cov: 27)

Exomes 𝑓: 0.12 ( 1961 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.693

Publications

3 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 -16 ACMG points.

BP6

Variant 11-22274548-CT-C is Benign according to our data. Variant chr11-22274548-CT-C is described in ClinVar as [Benign]. Clinvar id is 1174994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3 link	c.2236-10delT		intron_variant	Intron 19 of 21	ENST00000324559.9	NP_998764.1	Q75V66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9 link	c.2236-20delT		intron_variant	Intron 19 of 21	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.0515

AC:

7563

AN:

146856

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0324

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0387

Gnomad NFE

AF:

0.0666

Gnomad OTH

AF:

0.0415

GnomAD2 exomes

AF:

0.145

AC:

16715

AN:

115060

AF XY:

0.148

show subpopulations

Gnomad AFR exome

AF:

0.0717

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.0889

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.124

AC:

115698

AN:

929528

Hom.:

1961

Cov.:

AF XY:

0.124

AC XY:

57040

AN XY:

459084

show subpopulations

African (AFR)

AF:

0.0636

AC:

1404

AN:

22074

American (AMR)

AF:

0.0873

AC:

1972

AN:

22580

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

1461

AN:

14414

East Asian (EAS)

AF:

0.0656

AC:

1280

AN:

19516

South Asian (SAS)

AF:

0.103

AC:

5414

AN:

52572

European-Finnish (FIN)

AF:

0.169

AC:

5909

AN:

34920

Middle Eastern (MID)

AF:

0.0743

AC:

304

AN:

4090

European-Non Finnish (NFE)

AF:

0.129

AC:

93396

AN:

721770

Other (OTH)

AF:

0.121

AC:

4558

AN:

37592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

5300

10600

15900

21200

26500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0515

AC:

7561

AN:

146928

Hom.:

227

Cov.:

AF XY:

0.0515

AC XY:

3684

AN XY:

71574

show subpopulations

African (AFR)

AF:

0.0298

AC:

1205

AN:

40376

American (AMR)

AF:

0.0310

AC:

454

AN:

14636

Ashkenazi Jewish (ASJ)

AF:

0.0324

AC:

109

AN:

3364

East Asian (EAS)

AF:

0.000396

AC:

AN:

5048

South Asian (SAS)

AF:

0.0227

AC:

105

AN:

4630

European-Finnish (FIN)

AF:

0.106

AC:

1009

AN:

9482

Middle Eastern (MID)

AF:

0.0385

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0666

AC:

4407

AN:

66194

Other (OTH)

AF:

0.0413

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

348

696

1043

1391

1739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0439

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 03, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

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

- -

Miyoshi muscular dystrophy 3

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gnathodiaphyseal dysplasia

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.69

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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11-22274548-CTTTTT-CTTTT

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