ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7928-10T>C
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.
Uncertain significance(3); Benign(4); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000051.4(ATM):c.7928-10T>C
Variation ID: 127452 Accession: VCV000127452.26
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108333876 (GRCh38) [ NCBI UCSC ] 11: 108204603 (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 Aug 27, 2017 Jul 23, 2024 Jun 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.7928-10T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001330368.2:c.641-24805A>G intron variant NM_001351110.2:c.*38+1344A>G intron variant NM_001351834.2:c.7928-10T>C intron variant NC_000011.10:g.108333876T>C NC_000011.9:g.108204603T>C NG_009830.1:g.116045T>C NG_054724.1:g.140957A>G LRG_135:g.116045T>C LRG_135t1:c.7928-10T>C - Protein change
- Other names
- IVS53-10T>C
- Canonical SPDI
- NC_000011.10:108333875:T:C
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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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0.00060 (C)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00079
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00085
Trans-Omics for Precision Medicine (TOPMed) 0.00087
Exome Aggregation Consortium (ExAC) 0.00019
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00062
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
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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 |
10830 | 17425 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6577 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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May 29, 2018 | RCV000115258.23 | |
Conflicting interpretations of pathogenicity (6) |
criteria provided, conflicting classifications
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May 1, 2019 | RCV000588523.18 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 28, 2021 | RCV000776053.10 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV001083708.16 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001357331.9 | |
Benign (1) |
criteria provided, single submitter
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Jun 17, 2024 | RCV004589579.1 |
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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Benign
(May 01, 2019)
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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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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004222238.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
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Uncertain significance
(Sep 02, 2015)
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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: SCV000593491.1
First in ClinVar: Aug 27, 2017 Last updated: Aug 27, 2017 |
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Uncertain significance
(Feb 16, 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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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694365.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The ATM c.7928-10T>C variant involves the alteration of a conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal … (more)
Variant summary: The ATM c.7928-10T>C variant involves the alteration of a conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 23/121240 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.002033 (21/10330). This frequency is about 2 times the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Clinical diagnostic laboratories have classified this variant with conflicting classifications as uncertain significance (1) as well as benign (1). Therefore, this variant has been classified as a "Variant of Uncertain Significance - Possibly Benign." (less)
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Likely benign
(May 29, 2018)
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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: SCV000861178.1
First in ClinVar: Jul 06, 2018 Last updated: Jul 06, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Uncertain significance
(Oct 19, 2018)
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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: SCV000149167.15
First in ClinVar: May 17, 2014 Last updated: Apr 17, 2019 |
Comment:
This variant is denoted ATM c.7928-10T>C or IVS53-10T>C and consists of a T>C nucleotide substitution at the -10 position of intron 53 of the ATM … (more)
This variant is denoted ATM c.7928-10T>C or IVS53-10T>C and consists of a T>C nucleotide substitution at the -10 position of intron 53 of the ATM gene. In silico analyses, which include splice predictors and evolutionary conservation, are inconsistent in their assessment as to whether or not the variant is damaging. This variant has been reported in one individual with breast cancer (Decker 2017). ATM c.7928-10T>C was observed at an allele frequency of 0.23% (56/24,028) in individuals of African ancestry in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether ATM c.7928-10T>C is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. (less)
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Likely benign
(Sep 22, 2015)
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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: SCV000910677.1
First in ClinVar: May 20, 2019 Last updated: May 20, 2019 |
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Likely benign
(Jan 28, 2021)
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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: SCV002537778.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000252601.12
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
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Benign
(May 01, 2019)
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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: SCV001143121.1
First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020 |
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Benign
(Jun 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV005083980.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe … (more)
This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. (less)
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Likely 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: SCV001552773.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ATM c.7928-10T>C variant was not identified in the literature. The variant was identified in dbSNP (ID: rs188404773) as "With Uncertain significance allele", ClinVar (classified … (more)
The ATM c.7928-10T>C variant was not identified in the literature. The variant was identified in dbSNP (ID: rs188404773) as "With Uncertain significance allele", ClinVar (classified as benign by Invitae, as likely benign by EGL Genetic Diagnostics, and as uncertain significance by GeneDx, University of Chicago and Integrated Genetics), and in LOVD 3.0 (classified as likely benign by VKGL data sharing initiative).The variant was identified in control databases in 60 of 276948 chromosomes at a frequency of 0.0002 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 56 of 24028 chromosomes (freq: 0.002), Other in 1 of 6460 chromosomes (freq: 0.00016), Latino in 2 of 34418 chromosomes (freq: 0.00006), European Non-Finnish in 1 of 126484 chromosomes (freq: 0.000008), while the variant was not observed in the Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The ATM c.7928-10T>C variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. In addition, 0 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
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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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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: SCV002038450.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV002033984.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
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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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Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks. | Decker B | Journal of medical genetics | 2017 | PMID: 28779002 |
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATM | - | - | - | - |
Text-mined citations for rs188404773 ...
HelpRecord last updated Oct 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.