ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.4735C>T (p.Gln1579Ter)
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.4735C>T (p.Gln1579Ter)
Variation ID: 224518 Accession: VCV000224518.48
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108293436 (GRCh38) [ NCBI UCSC ] 11: 108164163 (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 Mar 20, 2016 Aug 4, 2024 Jan 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.4735C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Gln1579Ter nonsense NM_001351834.2:c.4735C>T NP_001338763.1:p.Gln1579Ter nonsense NC_000011.10:g.108293436C>T NC_000011.9:g.108164163C>T NG_009830.1:g.75605C>T LRG_135:g.75605C>T LRG_135t1:c.4735C>T LRG_135p1:p.Gln1579Ter - Protein change
- Q1579*
- Other names
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- Canonical SPDI
- NC_000011.10:108293435: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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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 |
10823 | 17415 |
Conditions - Germline
Condition
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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/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 24, 2021 | RCV000210197.12 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2023 | RCV000234068.16 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2017 | RCV000255389.22 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 24, 2024 | RCV004020572.1 |
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
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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
(Nov 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin:
germline
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University of Washington Department of Laboratory Medicine, University of Washington
Accession: SCV000266017.1
First in ClinVar: Mar 20, 2016 Last updated: Mar 20, 2016 |
Number of individuals with the variant: 1
Clinical Features:
breast cancer (present)
Age: 50-59 years
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Pathogenic
(Aug 25, 2017)
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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: SCV000322058.7
First in ClinVar: Oct 09, 2016 Last updated: Oct 09, 2016 |
Comment:
This variant is denoted ATM c.4735C>T at the cDNA level and p.Gln1579Ter (Q1579X) at the protein level. The substitution creates a nonsense variant, which changes … (more)
This variant is denoted ATM c.4735C>T at the cDNA level and p.Gln1579Ter (Q1579X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in the compound heterozygous state with a second ATM pathogenic variant in at least one individual with ataxia telangiectasia (R?be 2010, Hoche 2014), and in a woman with breast cancer and a family history of ovarian cancer (Shirts 2016). We consider this variant to be pathogenic. (less)
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Pathogenic
(Sep 08, 2023)
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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: SCV000282966.8
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 224518). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 224518). This premature translational stop signal has been observed in individual(s) with breast cancer and ataxia telangiectasia (PMID: 25037873, 26845104). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1579*) 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). (less)
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Pathogenic
(May 24, 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: SCV000273529.8
First in ClinVar: Mar 20, 2016 Last updated: May 01, 2024 |
Comment:
The p.Q1579* pathogenic mutation (also known as c.4735C>T), located in coding exon 30 of the ATM gene, results from a C to T substitution at … (more)
The p.Q1579* pathogenic mutation (also known as c.4735C>T), located in coding exon 30 of the ATM gene, results from a C to T substitution at nucleotide position 4735. This changes the amino acid from a glutamine to a stop codon within coding exon 30. This mutation has been reported in an individual with ataxia-telangiectasia, who also carried a second ATM mutation (Hoche F et al. Pediatr. Neurol. 2014 Sep;51:297-310). It was also identified in a patient with a personal history of breast cancer and a family history of ovarian cancer (Shirts BH et al. Genet. Med. 2016 Oct;18:974-81). 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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Likely pathogenic
(Dec 14, 2016)
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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: SCV000678088.1
First in ClinVar: Apr 16, 2017 Last updated: Apr 16, 2017 |
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Pathogenic
(Oct 27, 2020)
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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: SCV000913947.3
First in ClinVar: May 20, 2019 Last updated: Jun 19, 2021 |
Comment:
This variant changes 1 nucleotide in exon 31 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 31 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast cancer (PMID: 26845104) and in the compound heterozygous state with a second ATM mutation in an individual affected with ataxia telangiectasia (PMID: 25037873). 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
(Sep 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Baylor Genetics
Accession: SCV000807210.2
First in ClinVar: Apr 16, 2017 Last updated: Dec 11, 2022 |
Comment:
This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found twice in our laboratory in trans with a deleterious frameshift … (more)
This nonsense mutation is categorized as deleterious according to ACMG guidelines (PMID:18414213). It was found twice in our laboratory in trans with a deleterious frameshift mutation in a set of affected siblings. 9-year-old female & 12-year-old male sibs had cerebellar ataxia, oculomotor apraxia, intellectual disability, hypertonia, spasticity, peripheral neuropathy, pigmentary skin changes. (less)
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Pathogenic
(Feb 25, 2019)
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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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Revvity Omics, Revvity
Accession: SCV002018918.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Likely pathogenic
(Nov 01, 2017)
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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: SCV000692733.28
First in ClinVar: Oct 09, 2016 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 2
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Pathogenic
(Jan 24, 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: SCV004932870.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
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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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Improving performance of multigene panels for genomic analysis of cancer predisposition. | Shirts BH | Genetics in medicine : official journal of the American College of Medical Genetics | 2016 | PMID: 26845104 |
Ten new ATM alterations in Polish patients with ataxia-telangiectasia. | Podralska MJ | Molecular genetics & genomic medicine | 2014 | PMID: 25614872 |
Cognitive phenotype in ataxia-telangiectasia. | Hoche F | Pediatric neurology | 2014 | PMID: 25037873 |
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. | Huang Y | Neuromolecular medicine | 2013 | PMID: 23807571 |
DNA repair alterations in children with pediatric malignancies: novel opportunities to identify patients at risk for high-grade toxicities. | Rübe CE | International journal of radiation oncology, biology, physics | 2010 | PMID: 20153123 |
Text-mined citations for rs869312755 ...
HelpRecord last updated Sep 29, 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.