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

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1118 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

GnomAD3 exomes

AF:

0.0304

AC:

3497

AN:

115060

Hom.:

AF XY:

0.0295

AC XY:

1826

AN XY:

61940

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 SAS exome

AF:

0.0330

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

Gnomad4 AFR exome

AF:

0.0455

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.0297

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.0316

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0181

Gnomad4 OTH exome

AF:

0.0233

GnomAD4 genome

AF:

0.00760

AC:

1118

AN:

147054

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

506

AN XY:

71654

show subpopulations

Gnomad4 AFR

AF:

0.0223

Gnomad4 AMR

AF:

0.00450

Gnomad4 ASJ

AF:

0.00208

Gnomad4 EAS

AF:

0.0164

Gnomad4 SAS

AF:

0.000432

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.00447

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

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

- -

Feb 10, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

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

- -

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.

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