ClinVar Genomic variation as it relates to human health
NM_213599.3(ANO5):c.172C>T (p.Arg58Trp)
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.172C>T (p.Arg58Trp)
Variation ID: 197402 Accession: VCV000197402.72
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p14.3 11: 22218279 (GRCh38) [ NCBI UCSC ] 11: 22239825 (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 Jun 28, 2015 May 12, 2024 Mar 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_213599.3:c.172C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_998764.1:p.Arg58Trp missense NM_001142649.2:c.169C>T NP_001136121.1:p.Arg57Trp missense NC_000011.10:g.22218279C>T NC_000011.9:g.22239825C>T NG_015844.1:g.30104C>T LRG_868:g.30104C>T LRG_868t1:c.172C>T LRG_868p1:p.Arg58Trp Q75V66:p.Arg58Trp - Protein change
- R58W, R57W
- Other names
- NM_001142649.1(ANO5):c.169C>T(p.Arg57Trp)
- NM_213599.2(ANO5):c.172C>T(p.Arg58Trp)
- Canonical SPDI
- NC_000011.10:22218278:C: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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0.00020 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00009
1000 Genomes Project 30x 0.00016
The Genome Aggregation Database (gnomAD) 0.00016
1000 Genomes Project 0.00020
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
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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 |
1274 | 1309 |
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 (5) |
criteria provided, multiple submitters, no conflicts
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Mar 17, 2024 | RCV000178420.21 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Sep 7, 2023 | RCV000254777.37 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 18, 2024 | RCV000684805.9 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2021 | RCV001814090.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2022 | RCV002282002.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jun 3, 2020 | RCV001254062.7 |
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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Likely pathogenic
(Jan 22, 2015)
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criteria provided, single submitter
Method: clinical testing
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Muscular dystrophy, limb-girdle, type 2L
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000246418.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Likely pathogenic
(Dec 01, 2015)
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criteria provided, single submitter
Method: research
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: yes
Allele origin:
inherited
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Center for Genetic Medicine Research, Children's National Medical Center
Accession: SCV000265768.2
First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
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Likely pathogenic
(Sep 25, 2017)
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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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Athena Diagnostics
Accession: SCV000255642.3
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2018 |
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Pathogenic
(Sep 12, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000230495.5
First in ClinVar: Jun 28, 2015 Last updated: Oct 19, 2018 |
Number of individuals with the variant: 12
Sex: mixed
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Pathogenic
(Jun 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Miyoshi muscular dystrophy 3
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001522688.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
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Likely pathogenic
(Apr 15, 2020)
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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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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001714371.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Comment:
PS4_moderate, PM2, PM3
Number of individuals with the variant: 1
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Likely pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Abnormality of the musculature
Affected status: yes
Allele origin:
germline
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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755358.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Pathogenic
(Aug 09, 2022)
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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: SCV002571915.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: ANO5 c.172C>T (p.Arg58Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more)
Variant summary: ANO5 c.172C>T (p.Arg58Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251082 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ANO5 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (0.0001 vs 0.0047), allowing no conclusion about variant significance. c.172C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with Limb-Girdle Muscular Dystrophy and in individuals with elevated CK levels (e.g. Bouquet_2012, Schessl_2012, Witting_2013, Punetha_2016, Monies_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Thirteen ClinVar submitters have assessed the variant since 2014: one classified the variant as of uncertain significance, five as likely pathogenic, and seven as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Dec 06, 2023)
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criteria provided, single submitter
Method: curation
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Autosomal recessive limb-girdle muscular dystrophy type 2L
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV000803626.2
First in ClinVar: Dec 26, 2017 Last updated: Dec 09, 2023 |
Comment:
This variant is interpreted as Pathogenic, for Muscular dystrophy, limb-girdle, type 2L, autosomal recessive The following ACMG Tag(s) were applied: For recessive disorders, detected in … (more)
This variant is interpreted as Pathogenic, for Muscular dystrophy, limb-girdle, type 2L, autosomal recessive The following ACMG Tag(s) were applied: For recessive disorders, detected in trans with a pathogenic variant (PM3 upgraded to very strong; PMID: 22499103, 23041008, 23670307, 25864073, 25891276, 27671536, 32528171, 32925086, 36913258). Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3;). Well-established functional studies show a deleterious effect (PS3 downgraded to supporting; PMID: 33496727). (less)
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Pathogenic
(Jan 04, 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: SCV002017258.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 18, 2024)
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criteria provided, single submitter
Method: clinical testing
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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
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Invitae
Accession: SCV000645877.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 58 of the ANO5 protein … (more)
This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 58 of the ANO5 protein (p.Arg58Trp). This variant is present in population databases (rs201725369, gnomAD 0.05%). This missense change has been observed in individual(s) with distal myopathy and persistent asymptomatic hyperCK-emia (PMID: 22499103, 23041008, 23670307, 25891276, 27854218). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 197402). 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. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Mar 17, 2024)
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criteria provided, single submitter
Method: research
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Autosomal recessive limb-girdle muscular dystrophy type 2L
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004804731.2
First in ClinVar: Mar 30, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Feb 26, 2020)
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criteria provided, single submitter
Method: clinical testing
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Miyoshi muscular dystrophy 3
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
inherited
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001429972.1
First in ClinVar: Aug 21, 2020 Last updated: Aug 21, 2020 |
Clinical Features:
Elevated circulating creatine kinase concentration (present) , Cerebellar ataxia (present) , Hearing impairment (present) , Myalgia (present) , Diabetes mellitus (present)
Sex: female
Tissue: blood
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Likely pathogenic
(Mar 17, 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
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MGZ Medical Genetics Center
Accession: SCV002581464.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4_MOD, PM3, PM2_SUP, PP1, PP3
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Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Sep 07, 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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GeneDx
Accession: SCV000321403.10
First in ClinVar: Oct 09, 2016 Last updated: Sep 14, 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: 23041008, … (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: 23041008, 25891276, 22336395, 25864073, 27854218, 23670307, 22499103, 34426522, 32367299, 35239206, 32528171, 32925086, 33496727, 35032046, 35563815) (less)
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Pathogenic
(Apr 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: SCV001245644.21
First in ClinVar: May 09, 2020 Last updated: May 12, 2024 |
Comment:
ANO5: PM3:Very Strong, PM2, PM5
Number of individuals with the variant: 2
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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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Anoctamin-5 related muscle disease: clinical and genetic findings in a large European cohort. | de Bruyn A | Brain : a journal of neurology | 2023 | PMID: 36913258 |
ANO5 ensures trafficking of annexins in wounded myofibers. | Foltz SJ | The Journal of cell biology | 2021 | PMID: 33496727 |
Phenotypic Spectrum of Myopathies with Recessive Anoctamin-5 Mutations. | Vázquez J | Journal of neuromuscular diseases | 2020 | PMID: 32925086 |
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 Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases. | Punetha J | Journal of neuromuscular diseases | 2016 | PMID: 27854218 |
A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. | Monies D | Human genomics | 2016 | PMID: 27671536 |
Next generation sequencing on patients with LGMD and nonspecific myopathies: Findings associated with ANO5 mutations. | Savarese M | Neuromuscular disorders : NMD | 2015 | PMID: 25891276 |
Clinical and genetic features of anoctaminopathy in Saudi Arabia. | Bohlega S | Neurosciences (Riyadh, Saudi Arabia) | 2015 | PMID: 25864073 |
Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression. | Witting N | Journal of neurology | 2013 | PMID: 23670307 |
Dilated cardiomyopathy in patients with mutations in anoctamin 5. | Wahbi K | International journal of cardiology | 2013 | PMID: 23041008 |
Novel ANO5 mutations causing hyper-CK-emia, limb girdle muscular weakness and Miyoshi type of muscular dystrophy. | Schessl J | Muscle & nerve | 2012 | PMID: 22499103 |
Miyoshi-like distal myopathy with mutations in anoctamin 5 gene. | Bouquet F | Revue neurologique | 2012 | PMID: 22336395 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ANO5 | - | - | - | - |
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Text-mined citations for rs201725369 ...
HelpRecord last updated May 12, 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.