Genetic Variant ANO5:c.2236-10delT (chr11-22274548-CT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr11-22274548-CT-C is described in Lovd as [Benign]. Variant chr11-22274548-CT-C is described in Lovd as [Likely_benign]. Variant chr11-22274548-CT-C is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.145

AC:

16715

AN:

115060

Hom.:

236

AF XY:

0.148

AC XY:

9180

AN XY:

61940

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 SAS exome

AF:

0.136

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

Gnomad4 AFR exome

AF:

0.0636

Gnomad4 AMR exome

AF:

0.0873

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0656

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.0515

AC:

7561

AN:

146928

Hom.:

227

Cov.:

AF XY:

0.0515

AC XY:

3684

AN XY:

71574

show subpopulations

Gnomad4 AFR

AF:

0.0298

Gnomad4 AMR

AF:

0.0310

Gnomad4 ASJ

AF:

0.0324

Gnomad4 EAS

AF:

0.000396

Gnomad4 SAS

AF:

0.0227

Gnomad4 FIN

AF:

0.106

Gnomad4 NFE

AF:

0.0666

Gnomad4 OTH

AF:

0.0413

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

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.

11-22274548-CTTTTT-CTTTT

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