ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.6088A>G (p.Ile2030Val)
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_000051.4(ATM):c.6088A>G (p.Ile2030Val)
Variation ID: 133628 Accession: VCV000133628.47
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108315904 (GRCh38) [ NCBI UCSC ] 11: 108186631 (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 9, 2014 May 1, 2024 Mar 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.6088A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Ile2030Val missense NM_001330368.2:c.641-6833T>C intron variant NM_001351110.2:c.*39-6833T>C intron variant NM_001351834.2:c.6088A>G NP_001338763.1:p.Ile2030Val missense NC_000011.10:g.108315904A>G NC_000011.9:g.108186631A>G NG_009830.1:g.98073A>G NG_054724.1:g.158929T>C LRG_135:g.98073A>G LRG_135t1:c.6088A>G LRG_135p1:p.Ile2030Val - Protein change
- I2030V
- Other names
- p.I2030V:ATT>GTT
- NP_000042.3:p.Ile2030Val
- Canonical SPDI
- NC_000011.10:108315903:A:G
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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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0.00659 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00126
Exome Aggregation Consortium (ExAC) 0.00161
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00500
The Genome Aggregation Database (gnomAD) 0.00517
Trans-Omics for Precision Medicine (TOPMed) 0.00553
1000 Genomes Project 30x 0.00656
1000 Genomes Project 0.00659
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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ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10314 | 16610 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6280 |
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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Benign (8) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000120150.27 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2020 | RCV000129192.19 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000122865.37 | |
Benign (1) |
no assertion criteria provided
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- | RCV001357876.9 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV001573283.15 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 19, 2022 | RCV002225362.9 | |
Benign (1) |
criteria provided, single submitter
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Mar 21, 2022 | RCV003149823.9 | |
Benign (1) |
criteria provided, single submitter
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Jul 7, 2023 | RCV003315727.8 |
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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Benign
(Nov 23, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000246618.2
First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017 |
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Benign
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV001263993.1
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 rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000166123.14
First in ClinVar: Jun 15, 2014 Last updated: Feb 20, 2024 |
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Likely benign
(Feb 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV000576461.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
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Benign
(Aug 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000805592.1
First in ClinVar: Nov 10, 2017 Last updated: Nov 10, 2017 |
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Likely benign
(Apr 19, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
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National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002504744.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Number of individuals with the variant: 5
Geographic origin: South Africa
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Benign
(Dec 06, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000682300.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
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Benign
(Feb 24, 2022)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV002774008.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jan 16, 2019)
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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: SCV000167096.13
First in ClinVar: Jun 23, 2014 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 22995991, 11746755, 11505391, 24728327, 17517479, 11849780, 25980754)
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Benign
(Mar 21, 2022)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003837848.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
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Benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004024699.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
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Benign
(Jan 06, 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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157047.4
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Jan 07, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000230532.5
First in ClinVar: Jun 28, 2015 Last updated: Nov 10, 2017 |
Number of individuals with the variant: 2
Sex: mixed
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138535.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Benign
(Jul 07, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002537583.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Likely benign
(Aug 28, 2014)
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criteria provided, single submitter
Method: literature only
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Ataxia-telangiectasia syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220654.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004017292.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Benign
(Mar 01, 2024)
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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: SCV004811233.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
ATM: BP4, BS1, BS2
Number of individuals with the variant: 1
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Benign
(Jun 30, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000183931.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Likely benign
(Oct 26, 2017)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000787875.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
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: SCV001553470.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ATM p.Ile2030Val variant was identified in 5 of 3368 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer or lynch syndrome and … (more)
The ATM p.Ile2030Val variant was identified in 5 of 3368 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer or lynch syndrome and was present in 1 of 162 control chromosomes (Ho 2017, Iannuzzi 2002, Teraoka 2001, Yorczyk 2015, Yurgelun 2015). The variant was also identified in dbSNP (ID: rs145847315) as “With other allele”, ClinVar (as benign by Invitae, GeneDx, Ambry Genetics, EDL Genetic Diagnostics, University of Chicago, and Color Genomics, and as likely benign by Counsyl, and Institute for Biomarker Research), Clinvitae (4x), databases. The variant was not identified in Cosmic, MutDB, LOVD 3.0, or ATM-LOVD databases. The variant was identified in control databases in 444 of 277186 chromosomes (6 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 417 of 24038 chromosomes (freq: 0.02), Other in 4 of 6466 chromosomes (freq: 0.001), Latino in 19 of 34416 chromosomes (freq: 0.001), European in 4 of 126698 chromosomes (freq: 0.00003), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Ile2030 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
Number of individuals with the variant: 1
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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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: SCV001798915.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001457402.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808206.1 First in ClinVar: Aug 27, 2021 Last updated: Aug 27, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920406.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084291.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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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Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Use of panel tests in place of single gene tests in the cancer genetics clinic. | Yorczyk A | Clinical genetics | 2015 | PMID: 25318351 |
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy. | Ho AY | International journal of radiation oncology, biology, physics | 2007 | PMID: 17517479 |
ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects. | Iannuzzi CM | International journal of radiation oncology, biology, physics | 2002 | PMID: 11849780 |
Screening breast cancer patients for ATM mutations and polymorphisms by using denaturing high-performance liquid chromatography. | Atencio DP | Environmental and molecular mutagenesis | 2001 | PMID: 11746755 |
Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. | Teraoka SN | Cancer | 2001 | PMID: 11505391 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATM | - | - | - | - |
Text-mined citations for rs145847315 ...
HelpRecord last updated May 08, 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.