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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ClinVar Genomic variation as it relates to human health
NM_001097577.3(ANG):c.208A>G (p.Ile70Val)
Germline
Classification
Help
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.
(10)
Help
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.
Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(4)
Uncertain significance(2); Likely benign(4)
10
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001097577.3(ANG):c.208A>G (p.Ile70Val)
Variation ID: 18079 Accession: VCV000018079.20
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 20693772 (GRCh38) [ NCBI UCSC ] 14: 21161931 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Dec 6, 2016 Oct 8, 2024 Jan 19, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001097577.3:c.208A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001091046.1:p.Ile70Val missense NM_002937.5:c.-17-5583A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001145.4:c.208A>G NP_001136.1:p.Ile70Val missense NM_001282192.2:c.-18+122A>G intron variant NM_001282193.2:c.-17-5583A>G intron variant NM_001385271.1:c.208A>G NP_001372200.1:p.Ile70Val missense NM_001385272.1:c.208A>G NP_001372201.1:p.Ile70Val missense NM_001385273.1:c.208A>G NP_001372202.1:p.Ile70Val missense NM_001385274.1:c.208A>G NP_001372203.1:p.Ile70Val missense NM_194431.3:c.-18+4898A>G intron variant NC_000014.9:g.20693772A>G NC_000014.8:g.21161931A>G NG_008717.2:g.14596A>G NG_033053.1:g.14560A>G LRG_653:g.14596A>G LRG_653t1:c.208A>G LRG_653p1:p.Ile70Val P03950:p.Ile70Val - Protein change
- I70V
- Other names
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I46V
- Canonical SPDI
- NC_000014.9:20693771:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00020 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
Trans-Omics for Precision Medicine (TOPMed) 0.00060
Exome Aggregation Consortium (ExAC) 0.00061
The Genome Aggregation Database (gnomAD) 0.00073
The Genome Aggregation Database (gnomAD), exomes 0.00073
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| ANG | - | - |
GRCh38 GRCh37 |
8 | 127 | |
| EGILA | - | - | - | GRCh38 | - | 94 |
| RNASE4 | - | - |
GRCh38 GRCh37 |
- | 123 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Mar 31, 2020 | RCV000019705.35 | |
| Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
|
Jan 19, 2024 | RCV000335176.15 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 11, 2021 | RCV001659725.2 | |
|
ANG-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Dec 16, 2022 | RCV003974847.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Jan 19, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002419676.3
First in ClinVar: Apr 08, 2022 Last updated: Feb 28, 2024 |
|
|
|
Uncertain significance
(Nov 12, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000337060.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Number of individuals with the variant: 3
Sex: mixed
|
|
|
Uncertain significance
(Mar 31, 2020)
|
criteria provided, single submitter
Method: research
|
Amyotrophic lateral sclerosis type 9
Affected status: yes
Allele origin:
germline
|
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University
Accession: SCV001251007.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Number of individuals with the variant: 3
Geographic origin: Anatolian Peninsula
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Amyotrophic lateral sclerosis type 9
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001272127.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
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, … (more)
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(May 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001751941.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 29525178, 23665167, 23047679, 17900154, 18852347, 16501576, 23393617, 18087731, 22190368, 33875291)
|
|
|
Likely benign
(Jan 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Athena Diagnostics
Accession: SCV001880141.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
|
|
|
Pathogenic
(Oct 01, 2008)
|
no assertion criteria provided
Method: literature only
|
AMYOTROPHIC LATERAL SCLEROSIS 9
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000040003.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 22, 2019 |
Comment on evidence:
In 3 Scottish individuals with amyotrophic lateral sclerosis (ALS9; 611895), Greenway et al. (2006) identified a heterozygous 208A-G transition in the ANG gene, resulting in … (more)
In 3 Scottish individuals with amyotrophic lateral sclerosis (ALS9; 611895), Greenway et al. (2006) identified a heterozygous 208A-G transition in the ANG gene, resulting in an ile46-to-val (I46V) substitution. Two of the cases were familial. Gellera et al. (2008) identified the I46V mutation in 6 Italian ALS patients and 4 controls (0.8% in both groups), suggesting that it is a rare polymorphism in the Italian population. Paubel et al. (2008) identified the I46V mutation in 2 of 855 French patients with sporadic ALS. The mutation was found in 0.2% of healthy controls. (less)
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001929989.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001974436.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
|
Likely benign
(Dec 16, 2022)
|
no assertion criteria provided
Method: clinical testing
|
ANG-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004793105.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
Comment:
Comment:
This variant is associated with the following publications: (PMID: 29525178, 23665167, 23047679, 17900154, 18852347, 16501576, 23393617, 18087731, 22190368, 33875291)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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. |
Comment:
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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 29525178, 23665167, 23047679, 17900154, 18852347, 16501576, 23393617, 18087731, 22190368, 33875291)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Genetic investigation of amyotrophic lateral sclerosis patients in south Italy: a two-decade analysis. | Ungaro C | Neurobiology of aging | 2021 | PMID: 32951934 |
| Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database. | Tunca C | Human mutation | 2020 | PMID: 32579787 |
| A Novel Nonsense Angiogenin Mutation is Associated With Alzheimer Disease. | Gagliardi S | Alzheimer disease and associated disorders | 2019 | PMID: 30188356 |
| Twenty years of molecular analyses in amyotrophic lateral sclerosis: genetic landscape of Italian patients. | Lamp M | Neurobiology of aging | 2018 | PMID: 29525178 |
| Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers. | Dekker AM | Neurobiology of aging | 2016 | PMID: 26777436 |
| Genetic studies of Russian patients with amyotrophic lateral sclerosis. | Lysogorskaia EV | Amyotrophic lateral sclerosis & frontotemporal degeneration | 2015 | PMID: 26551617 |
| Fast prediction of deleterious angiogenin mutations causing amyotrophic lateral sclerosis. | Padhi AK | FEBS letters | 2013 | PMID: 23665167 |
| Pathophysiological insights into ALS with C9ORF72 expansions. | Williams KL | Journal of neurology, neurosurgery, and psychiatry | 2013 | PMID: 23463871 |
| Prediction of functional loss of human angiogenin mutants associated with ALS by molecular dynamics simulations. | Padhi AK | Scientific reports | 2013 | PMID: 23393617 |
| Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons. | Thiyagarajan N | Nature communications | 2012 | PMID: 23047679 |
| Contribution of major amyotrophic lateral sclerosis genes to the etiology of sporadic disease. | Lattante S | Neurology | 2012 | PMID: 22722621 |
| Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis. | van Es MA | Annals of neurology | 2011 | PMID: 22190368 |
| Angiogenin protects motoneurons against hypoxic injury. | Sebastià J | Cell death and differentiation | 2009 | PMID: 19444281 |
| Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis. | Fernández-Santiago R | Journal of neurology | 2009 | PMID: 19363631 |
| Mutations of the ANG gene in French patients with sporadic amyotrophic lateral sclerosis. | Paubel A | Archives of neurology | 2008 | PMID: 18852347 |
| Identification of new ANG gene mutations in a large cohort of Italian patients with amyotrophic lateral sclerosis. | Gellera C | Neurogenetics | 2008 | PMID: 18087731 |
| A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy. | Conforti FL | Neuromuscular disorders : NMD | 2008 | PMID: 17703939 |
| Characterization of human angiogenin variants implicated in amyotrophic lateral sclerosis. | Crabtree B | Biochemistry | 2007 | PMID: 17900154 |
| Variations in the coding and regulatory sequences of the angiogenin (ANG) gene are not associated to ALS (amyotrophic lateral sclerosis) in the Italian population. | Corrado L | Journal of the neurological sciences | 2007 | PMID: 17462671 |
| ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis. | Greenway MJ | Nature genetics | 2006 | PMID: 16501576 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ANG | - | - | - | - |
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Text-mined citations for rs121909541 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 13, 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.