ClinVar Genomic variation as it relates to human health
NM_213599.3(ANO5):c.692G>T (p.Gly231Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_213599.3(ANO5):c.692G>T (p.Gly231Val)
Variation ID: 2165 Accession: VCV000002165.93
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p14.3 11: 22236206 (GRCh38) [ NCBI UCSC ] 11: 22257752 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Apr 15, 2024 Feb 7, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_213599.3:c.692G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_998764.1:p.Gly231Val missense NM_001142649.2:c.689G>T NP_001136121.1:p.Gly230Val missense NC_000011.10:g.22236206G>T NC_000011.9:g.22257752G>T NG_015844.1:g.48031G>T LRG_868:g.48031G>T LRG_868t1:c.692G>T LRG_868p1:p.Gly231Val Q75V66:p.Gly231Val - Protein change
- G230V
- Other names
- G231V
- Canonical SPDI
- NC_000011.10:22236205:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00040 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00040
The Genome Aggregation Database (gnomAD) 0.00098
The Genome Aggregation Database (gnomAD), exomes 0.00103
1000 Genomes Project 30x 0.00047
Trans-Omics for Precision Medicine (TOPMed) 0.00116
Exome Aggregation Consortium (ExAC) 0.00105
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ANO5 | - | - |
GRCh38 GRCh37 |
1270 | 1305 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (7) |
criteria provided, multiple submitters, no conflicts
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Dec 12, 2022 | RCV000002249.23 | |
Pathogenic (11) |
criteria provided, multiple submitters, no conflicts
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Dec 22, 2023 | RCV000082853.47 | |
Pathogenic (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000369126.13 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jan 25, 2024 | RCV000627782.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 30, 2018 | RCV000825558.12 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000762830.10 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 4, 2024 | RCV003398417.5 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Mar 30, 2023 | RCV003993729.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 7, 2024 | RCV003993730.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jul 29, 2016)
|
criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000232828.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 28
Sex: mixed
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Pathogenic
(Aug 30, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Hereditary fructosuria
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966878.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
The p.Gly231Val variant in ANO5 has been previously reported in at least 15 comp ound heterozygous and 1 homozygous individuals with ANO5-related muscle diseases , … (more)
The p.Gly231Val variant in ANO5 has been previously reported in at least 15 comp ound heterozygous and 1 homozygous individuals with ANO5-related muscle diseases , ranging from asymptomatic hyperCKemia to limb-girdle muscular dystrophy type 2L (LGMD2L) or Miyoshi muscular dystrophy, and segregated with disease in one co mpound heterozygous sibling. Three of these individuals were female and presente d with asymptomatic hyperCKemia (Bolduc 2010, Wahbi 2013, Savarese 2015, Penttil a 2012, Witting 2013, Liewluck 2013, Sarkozy 2013). Typically, females have mil der disease manifestations than males (Bolduc 2010, Penttila 2012). This variant has also been reported in ClinVar (Variation ID 2165) and identified in 0.113% (143/126350) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant has been seen in the g eneral population, its frequency is low enough to be consistent with the disease prevalence. Computational prediction tools and conservation analysis suggest th at the p.Gly231Val variant may impact the protein. In summary, this variant meet s criteria to be classified as pathogenic for ANO5-related muscle diseases in an autosomal recessive manner based upon proband count. ACMG/AMP Criteria applied: PP3, PP1, PM3_Very Strong. (less)
Number of individuals with the variant: 1
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002058403.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000002165, PS1_S). The variant … (more)
Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000002165, PS1_S). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals(PMID: 25891276, 22402862, 23606453, 22980763, PM3_S). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000970, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Bicuspid aortic valve (present) , Elevated circulating creatine kinase concentration (present) , Genu valgum (present) , Lumbar hyperlordosis (present) , Mitral regurgitation (present) , Increased … (more)
Bicuspid aortic valve (present) , Elevated circulating creatine kinase concentration (present) , Genu valgum (present) , Lumbar hyperlordosis (present) , Mitral regurgitation (present) , Increased muscle fatiguability (present) , Pes planus (present) (less)
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Pathogenic
(Dec 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138251.2
First in ClinVar: Jan 09, 2020 Last updated: Dec 17, 2022 |
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Pathogenic
(Oct 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329637.9
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23193613, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23193613, 22402862, 23670307, 26810512, 30564623, 30919934, 33879512, 23047743, 22742934, 23041008, 25891276, 22980763, 20096397, 28489263, 31353849, 31931849, 31980526, 32399982, 34426522, 31589614, 32367299, 32528171, 32925086, 34008892, 32403337) (less)
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Pathogenic
(Dec 22, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002017247.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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ANO5-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004111816.2
First in ClinVar: Nov 20, 2023 Last updated: Mar 16, 2024 |
Comment:
The ANO5 c.692G>T variant is predicted to result in the amino acid substitution p.Gly231Val. This variant has been reported in several unrelated individuals to be … (more)
The ANO5 c.692G>T variant is predicted to result in the amino acid substitution p.Gly231Val. This variant has been reported in several unrelated individuals to be causative for limb girdle muscular dystrophy 2L (Bolduc et al. 2010. PubMed ID: 20096397; Wahbi et al. 2013. PubMed ID: 23041008; Savarese et al. 2015. PubMed ID: 25891276). In addition, we have seen this variant in the homozygous and compound heterozygous state in other patients at PreventionGenetics with muscular dystrophy. This variant is reported in 0.27% of alleles in individuals of Latino descent in gnomAD. In summary, we categorize the c.692G>T variant as pathogenic for autosomal recessive ANO5-related disorders. (less)
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Pathogenic
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001245647.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Comment:
ANO5: PM3:Very Strong, PM2, PP4, BP4
Number of individuals with the variant: 9
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Pathogenic
(Feb 07, 2024)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004813464.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
Variant summary: ANO5 c.692G>T (p.Gly231Val) results in a non-conservative amino acid change located in the Anoctamin, dimerisation domain (IPR032394) of the encoded protein sequence. Four … (more)
Variant summary: ANO5 c.692G>T (p.Gly231Val) results in a non-conservative amino acid change located in the Anoctamin, dimerisation domain (IPR032394) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.001 in 250958 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ANO5 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (0.001 vs 0.0047), allowing no conclusion about variant significance. c.692G>T has been reported in the literature in multiple bi-allelic individuals affected with muscular dystrophy type 2 (LGMD2), Miyoshi-like muscle dystrophy, and hyperCKemia (examples: Bolduc_2010, Wahbi_2013, Savarese_2015, TenDam_2019, and Gonzalez-Quereda_2020). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 20096397, 23041008, 30919934, 32403337, 25891276). ClinVar contains an entry for this variant (Variation ID: 2165). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Oct 08, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: yes
Allele origin:
paternal
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NeuroMeGen, Hospital Clinico Santiago de Compostela
Accession: SCV000882598.1
First in ClinVar: Feb 04, 2019 Last updated: Feb 04, 2019 |
|
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Gnathodiaphyseal dysplasia
Autosomal recessive limb-girdle muscular dystrophy type 2L Miyoshi muscular dystrophy 3
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893189.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
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Pathogenic
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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ANO5-Related Disorders
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000369971.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The ANO5 c.692G>T (p.Gly231Val) missense variant has been reported in five studies in which it is found in a total of nine individuals with ANO5-Related … (more)
The ANO5 c.692G>T (p.Gly231Val) missense variant has been reported in five studies in which it is found in a total of nine individuals with ANO5-Related Disorders, including in one individual in a homozygous state, in six individuals in a compound heterozygous state (including two siblings), in one individual in a heterozygous state in whom a second variant was not found, and in one individual in a heterozygous state as part of a complex allele with another missense variant (Bolduc et al. 2010; Wahbi et al. 2013; Penttilä et al. 2012; Sarkozy et al. 2012; Savarese et al. 2015). The p.Gly231Val variant was absent from 210 control chromosomes, but is reported at a frequency of 0.00402 in the Latino population of the Exome Aggregation Consortium. The Gly231 residue is conserved. Based on the collective evidence the p.Gly231Val variant is classified as pathogenic for ANO5-Related Disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Likely pathogenic
(Jul 15, 2022)
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criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002579896.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Jun 11, 2020)
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criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768606.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0108 - This gene is known to be associated with both recessive and dominant disease. Both dominant and recessive condition have been reported in this gene with no clear genotype and phenotype correlation (PMID: 25891276, PMID: 28176803). (N) 0200 - Variant is predicted to result in a missense amino acid change from a glycine to a valine (exon 8 of 22). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (272 heterozygotes, 0 homozygotes). (P) 0501 - Missense variant is highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif (dimerisation domain of Ca+-activated chloride-channel, anoctamin; PDB, NBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0801 - Strong previous evidence of pathogenicity in unrelated individuals. The variant has been previously reported in multiple patients with ANO5 -related myopathy, in a homozygous state or compound heterozygous with another variant (ClinVar, PMID: 31353849) (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
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Pathogenic
(Mar 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics Inc
Accession: SCV004229946.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with limb girdle muscular dystrophy. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Computational tools predict that this variant is damaging. (less)
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Likely pathogenic
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2L
Gnathodiaphyseal dysplasia
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000645882.10
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 231 of the ANO5 protein (p.Gly231Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 231 of the ANO5 protein (p.Gly231Val). This variant is present in population databases (rs137854523, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with limb-girdle muscular dystrophy type 2 (LGMD2), Miyoshi-like muscle dystrophy, and hyperCKemia (PMID: 20096397, 22402862, 22980763, 23041008, 23606453, 23670307, 25891276). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2165). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ANO5 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Likely pathogenic
(Mar 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Miyoshi muscular dystrophy 3
Affected status: unknown
Allele origin:
germline
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Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812391.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
This sequence change in ANO5 is predicted to replace glycine with valine at codon 231, p.(Gly231Val). The glycine residue is moderately conserved (100 vertebrates, UCSC), … (more)
This sequence change in ANO5 is predicted to replace glycine with valine at codon 231, p.(Gly231Val). The glycine residue is moderately conserved (100 vertebrates, UCSC), and is located in a cytoplasmic domain. There is a large physicochemical difference between glycine and valine. The highest population minor allele frequency in gnomAD v2.1 is 0.3% (95/35,372 alleles, 1 homozygote) in the Latino/admixed American population. This variant has been detected as homozygous or compound heterozygous with a second pathogenic allele in multiple individuals with limb-girdle muscular dystrophy, hyperCKaemia, and pseudo-metabolic myopathy phenotypes. The variants were confirmed in trans by parental testing in at least one of the compound heterozygous individuals (PMID: 20096397, 31353849). Multiple lines of computational evidence have conflicting predictions for the missense substitution (4/6 algorithms predict deleterious). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PM3_VeryStrong. (less)
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Pathogenic
(Feb 12, 2010)
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no assertion criteria provided
Method: literature only
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MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 12
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000022407.3
First in ClinVar: Apr 04, 2013 Last updated: Sep 28, 2018 |
Comment on evidence:
For discussion of the 692G-T transversion in exon 8 of the ANO5 gene, resulting in a gly231-to-val substitution (G231V) in the intracellular N-terminal tail, that … (more)
For discussion of the 692G-T transversion in exon 8 of the ANO5 gene, resulting in a gly231-to-val substitution (G231V) in the intracellular N-terminal tail, that was found in compound heterozygous state in a patient with limb-girdle muscular dystrophy type 2L (LGMDR12; 611307) and mild distal limb weakness by Bolduc et al. (2010), see 608662.0004. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798134.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808041.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743656.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001972085.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553936.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ANO5 p.G231V variant was identified as a compound heterozygous or homozygous variant in 17 of 1650 proband chromosomes (frequency: 0.01) from individuals with limb-girdle … (more)
The ANO5 p.G231V variant was identified as a compound heterozygous or homozygous variant in 17 of 1650 proband chromosomes (frequency: 0.01) from individuals with limb-girdle muscular dystrophy, hyperCKemia or mild dystrophic changes (Savarese_2015_PMID:25891276; Silva_2019_PMID:31353849; Bolduc_2010_PMID:20096397). The variant was identified in dbSNP (ID: rs137854523) and ClinVar (classified as pathogenic by GeneDx, Laboratory for Molecular Medicine and four other laboratories, and as likely pathogenic by Invitae and NeuroMeGen, Hospital Clinico Santiago de Compostela). The variant was identified in control databases in 274 of 282336 chromosomes (1 homozygous) at a frequency of 0.0009705 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Latino in 95 of 35372 chromosomes (freq: 0.002686), Other in 17 of 7204 chromosomes (freq: 0.00236), European (non-Finnish) in 152 of 128838 chromosomes (freq: 0.00118), Ashkenazi Jewish in 3 of 10360 chromosomes (freq: 0.00029), African in 5 of 24968 chromosomes (freq: 0.0002) and European (Finnish) in 2 of 25092 chromosomes (freq: 0.00008), but was not observed in the East Asian or South Asian populations. The p.Gly231 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
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ANO5 @LOVD
Accession: SCV000172430.1
First in ClinVar: Jul 23, 2014 Last updated: Jul 23, 2014 |
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no classification provided
Method: literature only
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000056226.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness. | Töpf A | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32528171 |
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain. | Gonzalez-Quereda L | Genes | 2020 | PMID: 32403337 |
Persistent asymptomatic or mild symptomatic hyperCKemia due to mutations in ANO5: the mildest end of the anoctaminopathies spectrum. | Panadés-de Oliveira L | Journal of neurology | 2020 | PMID: 32367299 |
The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease. | Bevilacqua JA | Orphanet journal of rare diseases | 2020 | PMID: 31931849 |
Clinical and molecular findings in a cohort of ANO5-related myopathy. | Silva AMS | Annals of clinical and translational neurology | 2019 | PMID: 31353849 |
Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients. | Ten Dam L | Clinical genetics | 2019 | PMID: 30919934 |
ANO5 Muscle Disease. | Adam MP | - | 2019 | PMID: 23193613 |
Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia. | Jin L | Scientific reports | 2017 | PMID: 28176803 |
Rhabdomyolysis featuring muscular dystrophies. | Lahoria R | Journal of the neurological sciences | 2016 | PMID: 26810512 |
Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations. | Savarese M | Neuromuscular disorders : NMD | 2015 | PMID: 25891276 |
Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression. | Witting N | Journal of neurology | 2013 | PMID: 23670307 |
ANO5-muscular dystrophy: clinical, pathological and molecular findings. | Liewluck T | European journal of neurology | 2013 | PMID: 23663589 |
ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. | Sarkozy A | Human mutation | 2013 | PMID: 23606453 |
Dilated cardiomyopathy in patients with mutations in anoctamin 5. | Wahbi K | International journal of cardiology | 2013 | PMID: 23041008 |
Muscle MRI findings in limb girdle muscular dystrophy type 2L. | Sarkozy A | Neuromuscular disorders : NMD | 2012 | PMID: 22980763 |
Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5. | Penttilä S | Neurology | 2012 | PMID: 22402862 |
Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. | Bolduc V | American journal of human genetics | 2010 | PMID: 20096397 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ANO5 | - | - | - | - |
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Text-mined citations for rs137854523 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.