11-22274548-CTTTTT-CT

Variant names:

• chr11-22274548-CTTTT-C
• rs72105710
• NM_213599.3:c.2236-13_2236-10delTTTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_213599.3(ANO5):​c.2236-13_2236-10delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,266,820 control chromosomes in the GnomAD database, including 7,620 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (965 hom., cov: 27)
  • Exomes 𝑓: 0.12 (6655 hom.)
• Consequence: ANO5 NM_213599.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.693
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-22274548-CTTTT-C is Benign according to our data. Variant chr11-22274548-CTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 96678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANO5	NM_213599.3	c.2236-13_2236-10delTTTT		intron_variant	Intron 19 of 21	ENST00000324559.9	NP_998764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANO5	ENST00000324559.9	c.2236-20_2236-17delTTTT		intron_variant	Intron 19 of 21	1	NM_213599.3	ENSP00000315371.9

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16140 AN: 147036 Hom.: 962 Cov.: 27

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0653

Gnomad EAS AF: 0.00138

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0903

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0968

GnomAD2 exomes AF: 0.160 AC: 18417 AN: 115060 AF XY: 0.164

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.00155

Gnomad FIN exome AF: 0.117

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.117 AC: 131055 AN: 1119710 Hom.: 6655 AF XY: 0.117 AC XY: 64590 AN XY: 553250

African (AFR) AF: 0.208 AC: 5372 AN: 25830

American (AMR) AF: 0.0622 AC: 1711 AN: 27504

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 1528 AN: 18296

East Asian (EAS) AF: 0.000735 AC: 21 AN: 28574

South Asian (SAS) AF: 0.126 AC: 7799 AN: 61918

European-Finnish (FIN) AF: 0.0877 AC: 3547 AN: 40444

Middle Eastern (MID) AF: 0.106 AC: 491 AN: 4640

European-Non Finnish (NFE) AF: 0.121 AC: 105154 AN: 866270

Other (OTH) AF: 0.117 AC: 5432 AN: 46234

GnomAD4 genome AF: 0.110 AC: 16149 AN: 147110 Hom.: 965 Cov.: 27 AF XY: 0.107 AC XY: 7695 AN XY: 71694

African (AFR) AF: 0.166 AC: 6693 AN: 40390

American (AMR) AF: 0.0672 AC: 985 AN: 14662

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 220 AN: 3368

East Asian (EAS) AF: 0.00139 AC: 7 AN: 5050

South Asian (SAS) AF: 0.102 AC: 474 AN: 4626

European-Finnish (FIN) AF: 0.0795 AC: 759 AN: 9542

Middle Eastern (MID) AF: 0.0839 AC: 24 AN: 286

European-Non Finnish (NFE) AF: 0.101 AC: 6676 AN: 66266

Other (OTH) AF: 0.0956 AC: 193 AN: 2018

Alfa AF: 0.0424 Hom.: 12

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 17, 2013

Eurofins Ntd Llc (ga)

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

- -

not provided Benign:1

Aug 18, 2019

GeneDx

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
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72105710; hg19: chr11-22296094;