ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7705_7706del (p.Arg2568_Asp2569insTer)
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
-
NM_000051.4(ATM):c.7705_7706del (p.Arg2568_Asp2569insTer)
Variation ID: 220550 Accession: VCV000220550.43
- Type and length
-
Microsatellite, 2 bp
- Location
-
Cytogenetic: 11q22.3 11: 108331951-108331952 (GRCh38) [ NCBI UCSC ] 11: 108202678-108202679 (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 Jul 11, 2016 Jun 17, 2024 Jan 31, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000051.4:c.7705_7706del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Arg2568_Asp2569insTer nonsense NM_000051.3:c.7702_7703delAG frameshift nonsense NM_000051.3:c.7705_7706del frameshift nonsense NM_000051.3:c.7705_7706delGA frameshift nonsense NM_001330368.2:c.641-22881_641-22880del intron variant NM_001351110.2:c.*38+3268_*38+3269del intron variant NM_001351834.2:c.7705_7706del NP_001338763.1:p.Arg2568_Asp2569insTer nonsense NC_000011.10:g.108331952GA[1] NC_000011.9:g.108202679GA[1] NG_009830.1:g.114121GA[1] NG_054724.1:g.142879CT[1] LRG_135:g.114121GA[1] LRG_135t1:c.7703_7704GA[1] LRG_135p1:p.Asp2569Terfs - Protein change
- Other names
- -
- Canonical SPDI
- NC_000011.10:108331950:AGAGA:AGA
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
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. |
|||
ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10833 | 17429 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6578 |
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. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Jan 27, 2024 | RCV000204947.28 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 18, 2022 | RCV000214581.19 | |
Pathogenic (1) |
criteria provided, single submitter
|
Aug 8, 2022 | RCV000478786.14 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV003468954.3 | |
Pathogenic (1) |
no assertion criteria provided
|
Jul 1, 2021 | RCV003165498.8 | |
Pathogenic (1) |
criteria provided, single submitter
|
Feb 8, 2023 | RCV003491961.1 |
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. |
|
---|---|---|---|---|---|
Likely pathogenic
(Nov 13, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914480.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The ATM c.7705_7706delGA (p.Asp2569Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Asp2569Ter variant has been reported in … (more)
The ATM c.7705_7706delGA (p.Asp2569Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The p.Asp2569Ter variant has been reported in three studies in which it was found in three individuals with ataxia telangiectasia (AT) (Teraoka et al. 1999; Mitui et al. 2003; Li et al. 2000). The variant was found in a compound heterozygous state in one Spanish individual in trans with a splice site variant, in a presumed compound heterozygous state with no second variant identified in a lymphoblastoid cell line derived from a patient with AT and in one of 268 AT chromosomes from a study of AT families in the US and Canada. The variant has also been reported with unspecified zygosity in one individual diagnosed with gastric cancer (Slavin et al. 2017). Control data are unavailable for the p.Asp2569Ter variant which is reported at a frequency of 0.000149 in the Latino population of the Genome Aggregation Database. Based on the evidence and potential impact of stop-gained variants, the p.Asp2569Ter variant is classified as likely pathogenic for ataxia telangiectasia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
Pathogenic
(Jan 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001478774.1
First in ClinVar: Feb 12, 2021 Last updated: Feb 12, 2021 |
Comment:
Variant summary: ATM c.7705_7706delGA (p.Asp2569X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: ATM c.7705_7706delGA (p.Asp2569X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2e-05 in 251176 control chromosomes. c.7705_7706delGA has been reported in the literature in individuals affected with Ataxia-Telangiectasia and other types of cancers (Teraoka_1999, Mitui_2003, Li_2000, Lu_2015, etc). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Likely pathogenic
(Mar 23, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000486046.2
First in ClinVar: Jul 11, 2016 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(Aug 08, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000565939.7
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Observed in the heterozygous state in individuals with a personal or family history of cancer consistent with pathogenic variants in this gene referred for genetic … (more)
Observed in the heterozygous state in individuals with a personal or family history of cancer consistent with pathogenic variants in this gene referred for genetic testing at GeneDx and in published literature (Quezada Urban et al., 2018; Lu et al., 2019); Observed with another pathogenic variant in ATM in unrelated patients with ataxia telangiectasia in published literature; however, it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Li et al., 2000; Mitui et al., 2003); Nonsense 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29025585, 10330348, 10817650, 12815592, 30128536, 30262796, 29625052, 26689913, 28888541, 29922827, 34871783, 34506673) (less)
|
|
Pathogenic
(Feb 25, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000682432.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant deletes 2 nucleotides in exon 52 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant deletes 2 nucleotides in exon 52 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 individuals affected with breast cancer (Color Health internal data), pancreatic cancer (PMID: 34506673; Color Health internal data), ovarian cancer (Color Health internal data), and gastric cancer (PMID: 29025585). This variant has also been reported in individuals affected with ataxia-telangiectasia (PMID: 10330348, 10817650, 12815592). This variant has been identified in 5/251176 chromosomes 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)
|
|
Pathogenic
(Jan 27, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000261175.11
First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Asp2569*) 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.Asp2569*) 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 present in population databases (rs759965045, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 10330348, 10817650, 12815592). This variant is also known as 7705delGA and 7704_7705delAG. ClinVar contains an entry for this variant (Variation ID: 220550). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Oct 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000275917.7
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The c.7705_7706delGA pathogenic mutation, located in coding exon 51 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 7705 to … (more)
The c.7705_7706delGA pathogenic mutation, located in coding exon 51 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 7705 to 7706, causing a translational frameshift with a predicted alternate stop codon (p.D2569*). This mutation has been identified in multiple families affected with ataxia-telangiectasia (A-T) (Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7; Mitui M et al. Hum. Mutat. 2003 Jul;22:43-50). This mutation was also detected during the analysis of 49 cell lines derived from individuals with A-T (Teraoka S et al. Am J Hum Genet. 1999 Jun;64(6):1617-31). 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)
|
|
Pathogenic
(Feb 08, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004239483.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004931148.1
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.
|
|
Pathogenic
(Jan 20, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004210104.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001462590.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
Pathogenic
(Jul 01, 2021)
|
no assertion criteria provided
Method: research
|
Gastric cancer
Affected status: unknown
Allele origin:
germline
|
Laboratory for Genotyping Development, RIKEN
Accession: SCV002758406.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
|
|
click to load more click to collapse |
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 |
---|---|---|---|---|
Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer. | Usui Y | The New England journal of medicine | 2023 | PMID: 36988593 |
Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma. | Walker EJ | The oncologist | 2021 | PMID: 34506673 |
Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network. | Slavin T | Cancer genetics | 2017 | PMID: 29025585 |
Patterns and functional implications of rare germline variants across 12 cancer types. | Lu C | Nature communications | 2015 | PMID: 26689913 |
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 |
Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate. | Mitui M | Human mutation | 2003 | PMID: 12815592 |
Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients. | Li A | American journal of medical genetics | 2000 | PMID: 10817650 |
Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. | Teraoka SN | American journal of human genetics | 1999 | PMID: 10330348 |
Comparative Study of the Treatment of Tuberculous Cervical Lymphadenitis with Special Reference of Streptomycin, P.A.S. and Isonicotinic Acid Hydrazide. | Almast SC | The Indian medical gazette | 1953 | PMID: 29015585 |
Text-mined citations for rs759965045 ...
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.