ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.3850del (p.Thr1284fs)
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.3850del (p.Thr1284fs)
Variation ID: 234124 Accession: VCV000234124.22
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108284329 (GRCh38) [ NCBI UCSC ] 11: 108155056 (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 17, 2017 Oct 8, 2024 Jan 23, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.3850del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Thr1284fs frameshift NM_000051.3:c.3849delA NM_000051.3:c.3850delA NM_001351834.2:c.3850del NP_001338763.1:p.Thr1284fs frameshift NC_000011.10:g.108284330del NC_000011.9:g.108155057del NG_009830.1:g.66499del LRG_135:g.66499del LRG_135t1:c.3850del LRG_135p1:p.Thr1284fs - Protein change
- T1284fs
- Other names
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- Canonical SPDI
- NC_000011.10:108284328:AA:A
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
10833 | 17429 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (2) |
criteria provided, multiple submitters, no conflicts
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Jun 28, 2021 | RCV000213614.8 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2024 | RCV000472137.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 2, 2020 | RCV000485880.3 | |
Pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001270927.1 | |
ATM-related disorder
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Pathogenic (1) |
no assertion criteria provided
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Feb 14, 2024 | RCV004547562.2 |
Pathogenic (1) |
criteria provided, single submitter
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Jan 23, 2024 | RCV004020698.1 |
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
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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
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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
(May 23, 2017)
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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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Counsyl
Accession: SCV000678110.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
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Pathogenic
(Sep 02, 2020)
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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: SCV000568320.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 17, 2019 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 9887333, 28492532, 21833744, 26822949, 29445900) (less)
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Pathogenic
(Jun 28, 2021)
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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: SCV001357926.3
First in ClinVar: Mar 25, 2020 Last updated: Jan 08, 2022 |
Comment:
This variant deletes 1 nucleotide in exon 26 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to … (more)
This variant deletes 1 nucleotide in exon 26 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in the homozygous or compound heterozygous state with an additional pathogenic ATM variant in individuals affected with ataxia-telangiectasia (PMID: 9887333, 21833744). This variant has also been reported in individuals affected with breast and pancreatic cancer (PMID: 26822949, 29445900). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
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Pathogenic
(Jan 16, 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: SCV000546898.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Thr1284Glnfs*9) in the ATM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Thr1284Glnfs*9) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and/or breast cancer (PMID: 9887333, 21833744, 26822949). ClinVar contains an entry for this variant (Variation ID: 234124). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 31, 2021)
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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: SCV000278636.8
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The c.3850delA pathogenic mutation, located in coding exon 25 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 3850, causing … (more)
The c.3850delA pathogenic mutation, located in coding exon 25 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 3850, causing a translational frameshift with a predicted alternate stop codon (p.T1284Qfs*9). This mutation (designated as 3849delA) has been identified in an individual with pancreatic cancer and detected homozygous in an individual with ataxia-telangiectasia (Lovecek M et al. Cancer Manag Res, 2019 Jan;11:599-609; Sandoval N et al. Hum. Mol. Genet. 1999 Jan; 8(1):69-79). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Jan 23, 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: SCV004932091.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
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Pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: case-control
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Breast and/or ovarian cancer
Affected status: no
Allele origin:
germline
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CZECANCA consortium
Accession: SCV001451731.1
First in ClinVar: Dec 24, 2020 Last updated: Dec 24, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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Pathogenic
(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: SCV001458197.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Pathogenic
(Feb 14, 2024)
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no assertion criteria provided
Method: clinical testing
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ATM-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004776524.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
The ATM c.3850delA variant is predicted to result in a frameshift and premature protein termination (p.Thr1284Glnfs*9). This variant was reported in individual(s) with ataxia-telangiectasia and/or … (more)
The ATM c.3850delA variant is predicted to result in a frameshift and premature protein termination (p.Thr1284Glnfs*9). This variant was reported in individual(s) with ataxia-telangiectasia and/or breast cancer (examples: Table 2, Soukupova J et al 2011. PubMed ID: 21833744; Table 1, Lhota F et al 2016. PubMed ID: 26822949). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/234124/). Frameshift variants in ATM are considered pathogenic. In summary, this variant is interpreted as pathogenic. (less)
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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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Genetic analysis of subsequent second primary malignant neoplasms in long-term pancreatic cancer survivors suggests new potential hereditary genetic alterations. | Lovecek M | Cancer management and research | 2019 | PMID: 30666157 |
Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients. | Lhota F | Clinical genetics | 2016 | PMID: 26822949 |
Ten new ATM alterations in Polish patients with ataxia-telangiectasia. | Podralska MJ | Molecular genetics & genomic medicine | 2014 | PMID: 25614872 |
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. | Huang Y | Neuromolecular medicine | 2013 | PMID: 23807571 |
Characterisation of ATM mutations in Slavic Ataxia telangiectasia patients. | Soukupova J | Neuromolecular medicine | 2011 | PMID: 21833744 |
Characterization of ATM gene mutations in 66 ataxia telangiectasia families. | Sandoval N | Human molecular genetics | 1999 | PMID: 9887333 |
Text-mined citations for rs876660865 ...
HelpRecord 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.