11-22227286-CTT-CT

Position:

• chr11-22227286-CTT-CT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.364-8del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 1,597,934 control chromosomes in the GnomAD database, including 9,229 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (4186 hom., cov: 30)
  • Exomes 𝑓: 0.027 (5043 hom.)
• Consequence: ANO5 NM_213599.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.00100

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-22227286-CT-C is Benign according to our data. Variant chr11-22227286-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 96684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-22227286-CT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANO5	NM_213599.3	c.364-8del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9	c.364-8del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_213599.3	ENSP00000315371	P2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20894 AN: 150926 Hom.: 4170 Cov.: 30

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0504

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.00492

Gnomad OTH AF: 0.107

GnomAD3 exomes AF: 0.0633 AC: 15241 AN: 240806 Hom.: 2258 AF XY: 0.0551 AC XY: 7192 AN XY: 130598

Gnomad AFR exome AF: 0.455

Gnomad AMR exome AF: 0.0321

Gnomad ASJ exome AF: 0.00881

Gnomad EAS exome AF: 0.226

Gnomad SAS exome AF: 0.0617

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.00537

Gnomad OTH exome AF: 0.0365

GnomAD4 exome AF: 0.0266 AC: 38520 AN: 1446888 Hom.: 5043 Cov.: 31 AF XY: 0.0259 AC XY: 18658 AN XY: 720078

Gnomad4 AFR exome AF: 0.458

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.00887

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.0585

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.00408

Gnomad4 OTH exome AF: 0.0530

GnomAD4 genome AF: 0.139 AC: 20955 AN: 151046 Hom.: 4186 Cov.: 30 AF XY: 0.136 AC XY: 10052 AN XY: 73750

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.0503

Gnomad4 ASJ AF: 0.00982

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.0730

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.00493

Gnomad4 OTH AF: 0.106

Asia WGS AF: 0.165 AC: 574 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 28, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Feb 11, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Miyoshi muscular dystrophy 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Limb-girdle muscular dystrophy, recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2016

This variant is associated with the following publications: (PMID: 23606453) -

Gnathodiaphyseal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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 31, 2024

- -

Autosomal recessive limb-girdle muscular dystrophy type 2L Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Miyoshi myopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs146983312; hg19: chr11-22248832;