11-22279669-C-G

Position:

chr11-22279669-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_213599.3(ANO5):c.2646C>G(p.Asn882Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,612,758 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 36 hom., cov: 32)

Exomes 𝑓: 0.00095 ( 20 hom. )

Consequence

ANO5
NM_213599.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: -0.286

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:

ANO5 (HGNC:):

ANO5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004618734).

BP6

Variant 11-22279669-C-G is Benign according to our data. Variant chr11-22279669-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 128390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22279669-C-G is described in Lovd as [Pathogenic].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1530/151830) while in subpopulation AFR AF= 0.0352 (1461/41464). AF 95% confidence interval is 0.0337. There are 36 homozygotes in gnomad4. There are 704 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1530 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO5	NM_213599.3 linkuse as main transcript	c.2646C>G	p.Asn882Lys	missense_variant	22/22	ENST00000324559.9	NP_998764.1	Q75V66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9 linkuse as main transcript	c.2646C>G	p.Asn882Lys	missense_variant	22/22	1	NM_213599.3	ENSP00000315371.9		Q75V66

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1531

AN:

151714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0353

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00335

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00719

GnomAD3 exomes

AF:

0.00251

AC:

631

AN:

250920

Hom.:

AF XY:

0.00170

AC XY:

230

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.000949

AC:

1387

AN:

1460928

Hom.:

Cov.:

AF XY:

0.000772

AC XY:

561

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.00191

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00172

GnomAD4 genome

AF:

0.0101

AC:

1530

AN:

151830

Hom.:

Cov.:

AF XY:

0.00948

AC XY:

704

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.00328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.000517

Hom.:

Bravo

AF:

0.0115

ESP6500AA

AF:

0.0386

AC:

170

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00315

AC:

383

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 26, 2015	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2Other:1

not provided, no classification provided	literature only	ANO5 @LOVD	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 14, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Gnathodiaphyseal dysplasia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Miyoshi muscular dystrophy 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

ANO5-Related Muscle Diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 28, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.0

DANN

Benign

0.87

DEOGEN2

Benign

0.034

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

REVEL

Benign

0.13

Sift

Benign

0.70

Sift4G

Benign

0.77

Polyphen

0.10

Vest4

0.64

MutPred

0.14

Gain of ubiquitination at N882 (P = 0.0289);

MVP

0.17

MPC

0.099

ClinPred

0.0059

GERP RS

-4.8

Varity_R

0.061

gMVP

0.40

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