11-22274548-CTTTTT-CTTTTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_213599.3(ANO5):c.2236-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,154,642 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 10 hom., cov: 27)

Exomes 𝑓: 0.021 ( 6 hom. )

Consequence

ANO5
NM_213599.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

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-C-CT is Benign according to our data. Variant chr11-22274548-C-CT is described in ClinVar as [Benign]. Clinvar id is 195544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0076 (1118/147054) while in subpopulation AFR AF = 0.0223 (901/40388). AF 95% confidence interval is 0.0211. There are 10 homozygotes in GnomAd4. There are 506 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3 link	c.2236-10dupT		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.2236-21_2236-20insT		intron_variant	Intron 19 of 21	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.00758

AC:

1114

AN:

146982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00208

Gnomad EAS

AF:

0.0164

Gnomad SAS

AF:

0.000431

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00968

Gnomad NFE

AF:

0.000574

Gnomad OTH

AF:

0.00450

GnomAD2 exomes

AF:

0.0304

AC:

3497

AN:

115060

AF XY:

0.0295

show subpopulations

Gnomad AFR exome

AF:

0.0461

Gnomad AMR exome

AF:

0.0532

Gnomad ASJ exome

AF:

0.0457

Gnomad EAS exome

AF:

0.0872

Gnomad FIN exome

AF:

0.0214

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0373

GnomAD4 exome

AF:

0.0211

AC:

21236

AN:

1007588

Hom.:

Cov.:

AF XY:

0.0210

AC XY:

10468

AN XY:

498356

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0455

AC:

1072

AN:

23556

American (AMR)

AF:

0.0328

AC:

821

AN:

25008

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

480

AN:

16178

East Asian (EAS)

AF:

0.0481

AC:

1138

AN:

23652

South Asian (SAS)

AF:

0.0316

AC:

1792

AN:

56792

European-Finnish (FIN)

AF:

0.0189

AC:

708

AN:

37442

Middle Eastern (MID)

AF:

0.0313

AC:

135

AN:

4316

European-Non Finnish (NFE)

AF:

0.0181

AC:

14121

AN:

779110

Other (OTH)

AF:

0.0233

AC:

969

AN:

41534

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

3069

6138

9208

12277

15346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00760

AC:

1118

AN:

147054

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

506

AN XY:

71654

show subpopulations

African (AFR)

AF:

0.0223

AC:

901

AN:

40388

American (AMR)

AF:

0.00450

AC:

AN:

14658

Ashkenazi Jewish (ASJ)

AF:

0.00208

AC:

AN:

3364

East Asian (EAS)

AF:

0.0164

AC:

AN:

5050

South Asian (SAS)

AF:

0.000432

AC:

AN:

4634

European-Finnish (FIN)

AF:

0.000945

AC:

AN:

9520

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000574

AC:

AN:

66238

Other (OTH)

AF:

0.00447

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00575

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 10, 2015

Eurofins Ntd Llc (ga)

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

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 06, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 03, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

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

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

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

(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-CTTTTTT

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