This c.7638_7646del (p.Arg2547_Ser2549del) has previously been reported in compound heterozygous and homozygous patients with ataxia telangiectasia [PMID 8808599]. Functional assays showed that the variant does not affect the level of ATM protein but does reduce the level of kinase activity [PMID 19431188]. A mouse model carrying this deletion has an increase susceptibility to develop tumors [reported as 7636del9 in PMID 12195425]. This variant was further detected in 12 out of 294 families with breast cancer. However, the difference in tumor incidence between carrier and non carrier was not statistically significant. However, this variant was detected in another patient with breast cancer [PMID 8797579]. This c.7638_7646del (p.Arg2547_Ser2549del) variant has not been observed the ExAC population database and has been observed in one individual in our internal database. It is thus interpreted as a likely pathogenic variant.
ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7638_7646del (p.Arg2547_Ser2549del)
Germline
Classification
Help
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.
(24)
Help
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.
Pathogenic/Likely pathogenic
24
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000051.4(ATM):c.7638_7646del (p.Arg2547_Ser2549del)
Variation ID: 3019 Accession: VCV000003019.92
- Type and length
-
Deletion, 9 bp
- Location
-
Cytogenetic: 11q22.3 11: 108331885-108331893 (GRCh38) [ NCBI UCSC ] 11: 108202612-108202620 (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 5, 2015 Oct 20, 2024 Mar 23, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000051.4:c.7638_7646del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Arg2547_Ser2549del inframe deletion NM_000051.4:c.7638_7646delTAGAATTTC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe deletion NM_001330368.2:c.641-22822_641-22814del intron variant NM_001351110.2:c.*38+3327_*38+3335del intron variant NM_001351834.2:c.7638_7646del NP_001338763.1:p.Arg2547_Ser2549del inframe deletion NC_000011.10:g.108331887_108331895del NC_000011.9:g.108202614_108202622del NG_009830.1:g.114056_114064del NG_054724.1:g.142940_142948del LRG_135:g.114056_114064del LRG_135t1:c.7638_7646del LRG_135p1:p.Arg2547_Ser2549del - Protein change
- -
- Other names
-
7637del9
delSRI
- Canonical SPDI
- NC_000011.10:108331884:TCTAGAATTTC:TC
-
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.
- -
- Links
- Comment on variant
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 |
10839 | 17439 | |
| C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6582 |
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 (1) |
no assertion criteria provided
|
Sep 1, 2002 | RCV000003163.15 | |
| Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000206671.33 | |
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 7, 2023 | RCV000212075.43 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Aug 1, 2016 | RCV000417362.10 | |
| Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 23, 2024 | RCV000709706.14 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Feb 27, 2023 | RCV000185637.24 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 7, 2021 | RCV001797988.12 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV001355331.11 | |
|
ATM-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Jun 17, 2024 | RCV004547454.3 |
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
(Apr 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839880.1
First in ClinVar: Oct 14, 2018 Last updated: Oct 14, 2018 |
Comment:
This c.7638_7646del (p.Arg2547_Ser2549del) has previously been reported in compound heterozygous and homozygous patients with ataxia telangiectasia [PMID 8808599]. Functional assays showed that the variant does … (more)
This c.7638_7646del (p.Arg2547_Ser2549del) has previously been reported in compound heterozygous and homozygous patients with ataxia telangiectasia [PMID 8808599]. Functional assays showed that the variant does not affect the level of ATM protein but does reduce the level of kinase activity [PMID 19431188]. A mouse model carrying this deletion has an increase susceptibility to develop tumors [reported as 7636del9 in PMID 12195425]. This variant was further detected in 12 out of 294 families with breast cancer. However, the difference in tumor incidence between carrier and non carrier was not statistically significant. However, this variant was detected in another patient with breast cancer [PMID 8797579]. This c.7638_7646del (p.Arg2547_Ser2549del) variant has not been observed the ExAC population database and has been observed in one individual in our internal database. It is thus interpreted as a likely pathogenic variant. (less)
|
|
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Pathogenic
(Aug 31, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000331662.4
First in ClinVar: Dec 06, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Pathogenic
(Oct 27, 2017)
|
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: SCV000916557.1
First in ClinVar: May 31, 2019 Last updated: May 31, 2019 |
Comment:
Variant summary: The ATM c.7638_7646delTAGAATTTC (p.Arg2547_Ser2549del) variant involves the inframe deletion of 9 nucleotides located in the PIK-related kinase domain (IPR014009) (InterPro). One in silico … (more)
Variant summary: The ATM c.7638_7646delTAGAATTTC (p.Arg2547_Ser2549del) variant involves the inframe deletion of 9 nucleotides located in the PIK-related kinase domain (IPR014009) (InterPro). One in silico tool predicts a damaging outcome for this variant. Functional studies confirmed that there is no detectable ATM kinase activity associated with this variant and that LCLs with this variant exhibited p53, p21, and MDM2 response that was indistinguishable from classical A-T (Stewart_2001). This variant was found in 5/246251 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528). This variant was reported in multiple AT patients (Stankovic_1998, Skowronska_2012, Stewart_2001). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
|
|
|
Likely pathogenic
(Dec 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: yes
Allele origin:
germline
|
AiLife Diagnostics, AiLife Diagnostics
Accession: SCV002502830.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
Number of individuals with the variant: 1
Secondary finding: no
|
|
|
Pathogenic
(Apr 29, 2021)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002538126.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The ATM c.7638_7646delTAGAATTTC (p.R2547_S2549del) variant has been reported in individuals with ataxia-telangiectasia and breast cancer (PMID: 22649200, 21787400, 11382771, 8797579). This change results in a … (more)
The ATM c.7638_7646delTAGAATTTC (p.R2547_S2549del) variant has been reported in individuals with ataxia-telangiectasia and breast cancer (PMID: 22649200, 21787400, 11382771, 8797579). This change results in a deletion of three amino acids without altering the integrity of the reading frame. Functional studies demonstrated complete loss of ATM kinase function and impairment of cellular response to ionizing radiation (PMID: 19431188, 11382771). The variant was observed in 7/251148 chromosomes in the large and broad cohorts of the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID 3019). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
|
|
|
|
Pathogenic
(Sep 20, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556947.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Dec 07, 2021)
|
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: SCV002042923.2
First in ClinVar: Jan 03, 2022 Last updated: Mar 11, 2023 |
|
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000262210.12
First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024 |
Comment:
This variant, c.7638_7646del, results in the deletion of 3 amino acid(s) of the ATM protein (p.Arg2547_Ser2549del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.7638_7646del, results in the deletion of 3 amino acid(s) of the ATM protein (p.Arg2547_Ser2549del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587776547, gnomAD 0.007%). This variant has been observed in individuals with breast cancer and ataxia-telangiectasia (PMID: 7792600, 8797579, 11382771, 12552559, 21787400, 22649200). This variant is also known as 7636del9 and 7638del9. ClinVar contains an entry for this variant (Variation ID: 3019). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ATM function (PMID: 11382771, 12195425, 19431188, 22649200). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Likely 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: SCV004932506.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 10817650]. Functional studies indicate … (more)
This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 10817650]. Functional studies indicate this variant impacts protein function [PMID: 19431188]. (less)
|
|
|
Pathogenic
(Dec 15, 2020)
|
criteria provided, single submitter
Method: research
|
Familial cancer of breast
Affected status: no
Allele origin:
germline
|
Department of Pediatrics, Memorial Sloan Kettering Cancer Center
Accession: SCV001478108.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
|
|
|
Pathogenic
(Sep 26, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000487009.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Mar 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000209607.17
First in ClinVar: Feb 24, 2015 Last updated: Mar 18, 2023 |
Comment:
Observed in the heterozygous state in individuals with ATM-related cancers (Vorechovsky et al., 1996; Goldgar et al., 2011; Bunnell et al., 2017; Decker et al., … (more)
Observed in the heterozygous state in individuals with ATM-related cancers (Vorechovsky et al., 1996; Goldgar et al., 2011; Bunnell et al., 2017; Decker et al., 2017; Na et al., 2017; Lu et al., 2019); Published functional studies demonstrate a damaging effect: absence of kinase activity and reduced ATM protein expression (Stewart et al., 2001; Barone et al., 2009; Reiman et al., 2011); In-frame deletion of 3 amino acids in a non-repeat region predicted to critically alter the protein; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as c.7636del9 and 7638del9; This variant is associated with the following publications: (PMID: 25038946, 12552559, 21787400, 10817650, 19781682, 26556299, 32866655, 29922827, 8789452, 21792198, 9537233, 19431188, 11382771, 22649200, 21933854, 10330348, 8808599, 27276934, 8797579, 8845835, 7792600, 15279808, 12195425, 28779002, 27989354, 30128536, 34308366, 26896183, 31447099, 31948886, 32853339, 32338768, 34308104, 33804961, 23532176, 9150358, 9463314) (less)
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|
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Pathogenic
(Feb 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000682427.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant causes an in-frame deletion of 3 amino acids in the ATM protein. This variant is also known as 7636del9, 7637del9 and delSRI in … (more)
This variant causes an in-frame deletion of 3 amino acids in the ATM protein. This variant is also known as 7636del9, 7637del9 and delSRI in the literature. Functional studies have reported the mutant protein to show a severely defective kinase activity (PMID: 11382771, 19431188, 21778326, 22649200). This variant has been reported in over ten heterozygous individuals affected with breast cancer (PMID: 9288106, 16652348, 21787400; Color internal data) and pancreatic cancer (PMID: 33439686; Color internal data). This variant has been observed in homozygous and compound heterozygous states in over a dozen individuals affected with autosomal recessive ataxia-telangiectasia, indicating that this variant contributes to disease (PMID: 7792600, 8755918, 8845835, 8808599, 9443866, 9463314, 10817650). This variant is reported to be a founder mutation in individuals of Irish and British ancestry (PMID: 9443866, 9463314). This variant has been identified in 7/251148 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jul 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186502.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The c.7638_7646delTAGAATTTC pathogenic mutation (also known as p.R2547_S2549del), located in coding exon 51 of the ATM gene, results from an in-frame deletion of 9 nucleotides … (more)
The c.7638_7646delTAGAATTTC pathogenic mutation (also known as p.R2547_S2549del), located in coding exon 51 of the ATM gene, results from an in-frame deletion of 9 nucleotides between positions 7638 and 7646. This results in the deletion of 3 amino acids between codons 2547 and 2549. This pathogenic mutation has been reported in individuals diagnosed with breast cancer, some of whom also had family histories of other cancers (Vorechovsky I et al. Cancer Res. 1996 Sep;56:4130-3; Goldgar DE et al. Breast Cancer Res. 2011 Jul;13:R73). In addition, this mutation has been reported in a homozygous state and in conjunction with other deleterious ATM mutations in multiple individuals and/or families with ataxia-telagiectasia (Gilad S et al. Hum. Mol. Genet. 1996 Apr;5:433-9; Wright J et al. Am. J. Hum. Genet. 1996 Oct;59:839-46; Watters D et al. Oncogene. 1997 Apr;14:1911-21; Telatar M et al. Am. J. Hum. Genet. 1998 Jan;62:86-97; Stankovic T et al. Am. J. Hum. Genet. 1998 Feb;62:334-45; Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7; Buzin C et al. Hum. Mutat. 2003 Feb;21:123-31). Further, functional analysis has shown that this mutation results in intact ATM protein expression but no kinase activity (Stewart GS et al. J. Biol. Chem. 2001 Aug;276:30133-41). Of note, this alteration is also designated as 7636del9, 2546delSRI, 7638del9 and 7638_7646del9 in published literature. Based on the available evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Mar 23, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004204412.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001961311.20
First in ClinVar: Oct 08, 2021 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jun 23, 1995)
|
no assertion criteria provided
Method: literature only
|
ATAXIA-TELANGIECTASIA, COMPLEMENTATION GROUP E
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000023313.2
First in ClinVar: Apr 04, 2013 Last updated: Jul 05, 2015 |
Comment on evidence:
In an Australian family of Irish/British ethnic extraction, Savitsky et al. (1995) found that 2 sibs with ataxia-telangiectasia of complementation group E (ATE; 208900) were … (more)
In an Australian family of Irish/British ethnic extraction, Savitsky et al. (1995) found that 2 sibs with ataxia-telangiectasia of complementation group E (ATE; 208900) were homozygous for deletion of 9 bp, resulting in a loss of amino acids 1198-1200 in the gene product. The typing of these patients (AT1ABR and AT2ABR) was performed by Chen et al. (1984). (less)
|
|
|
Pathogenic
(Jan 05, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002080799.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
|
Likely pathogenic
(Jan 24, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV002506605.1
First in ClinVar: May 07, 2022 Last updated: May 07, 2022 |
|
|
|
Pathogenic
(Sep 01, 2002)
|
no assertion criteria provided
Method: literature only
|
T-CELL PROLYMPHOCYTIC LEUKEMIA, SOMATIC
Affected status: not provided
Allele origin:
somatic
|
OMIM
Accession: SCV000023321.3
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
The most frequent variant of the ATM gene detected out of 30 ataxia-telangiectasia (AT; 208900) mutant lines studied by Wright et al. (1996) was a … (more)
The most frequent variant of the ATM gene detected out of 30 ataxia-telangiectasia (AT; 208900) mutant lines studied by Wright et al. (1996) was a 9-bp deletion at codon 2546 in exon 54. The deletion was detected by them in 3 unrelated patients and had been previously reported in 5 different patients, corresponding to 8% of the mutations reported at that time. This same mutation was identified by Vorechovsky et al. (1997) in tumor tissue from a sporadic case of T-cell prolymphocytic leukemia (TPLL), a rare clonal malignancy with similarities to a mature T-cell leukemia seen in ataxia-telangiectasia. This mutation was identified in heterozygous form in a female breast cancer patient with a family history of multiple malignancies (Vorechovsky et al., 1996). The deleted sequence is 5-prime-TCTAGAATT-3-prime. Spring et al. (2002) demonstrated the appearance of tumors in 6 humans, from 12 families, who were heterozygous for the 7636del9 mutation. In parallel, they showed that 'knock-in' heterozygous mice harboring an in-frame deletion corresponding to the human 7636del9 mutation showed increased susceptibility to tumors. The 7636del9 mutation had a dominant-negative effect in control cells, inhibiting radiation-induced ATM kinase activity in vivo and in vitro. (less)
|
|
|
Pathogenic
(Jun 17, 2024)
|
no assertion criteria provided
Method: clinical testing
|
ATM-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805616.4
First in ClinVar: Sep 13, 2018 Last updated: Oct 08, 2024 |
Comment:
The ATM c.7638_7646del9 variant is predicted to result in an in-frame deletion (p.Arg2547_Ser2549del). This variant is also known in the literature as c.7636del9. This variant … (more)
The ATM c.7638_7646del9 variant is predicted to result in an in-frame deletion (p.Arg2547_Ser2549del). This variant is also known in the literature as c.7636del9. This variant has been reported in patients with ataxia telangiectasia (Savitsky et al. 1995. PubMed ID: 7792600), prostate cancer (Supplemental Table 1 in Na et al. 2017. PubMed ID: 27989354), and breast cancer (Vorechovský et al. 1996. PubMed ID: 8797579; Chen et al. 1998. PubMed ID: 9537233; Lu et al. 2019. PubMed ID: 30128536, eTable 12; Goldgar et al. 2011. PubMed ID: 21787400). In vitro functional analysis showed that this variant had no kinase activity (Barone et al. 2009. PubMed ID: 19431188). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD and is interpreted as likely pathogenic/pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3019/). This variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Oct 27, 2016)
|
no assertion criteria provided
Method: literature only
|
Ataxia-telangiectasia syndrome
Affected status: yes
Allele origin:
germline
|
GeneReviews
Accession: SCV000328309.1
First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
Geographic origin: United Kingdom
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|
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Uncertain significance
(Aug 01, 2016)
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no assertion criteria provided
Method: research
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Breast cancer
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
CSER _CC_NCGL, University of Washington
Study: CSER - NEXT Medicine variant annotation
Accession: SCV000503545.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Found in a male patient having exome sequencing for an unrelated indication. No known personal or family history of breast cancer.
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|
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Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001550193.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ATM p.Arg2547_Ser2549del variant was identified in 14 of 6042 proband chromosomes (frequency: 0.002) from individuals or families with Ataxia-telangiectasia and breast cancer (Buzin 2003, … (more)
The ATM p.Arg2547_Ser2549del variant was identified in 14 of 6042 proband chromosomes (frequency: 0.002) from individuals or families with Ataxia-telangiectasia and breast cancer (Buzin 2003, Goldgar 2011, Li 2000, Reiman 2011). The variant was also identified in the following databases: dbSNP (ID: rs587776547) as "With Pathogenic allele", ClinVar (9x pathogenic, 1x uncertain significance), Clinvitae (5x pathogenic, 1x uncertain significance), Cosmic (1x, haematopoietic and lymphoid tumour), and the LOVD 3.0 (27x). The variant was not identified in the MutDB database. The variant was not identified in the control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). Multiple functional studies have shown the ATM protein lacks kinase activity and is expressed at low levels, confirming the pathogenicity of this variant (Barone 2009, Reiman 2011). This variant is an in-frame deletion resulting in the removal of three residues, from codon 2547 to 2549. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic. (less)
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Comment:
Comment:
Variant summary: The ATM c.7638_7646delTAGAATTTC (p.Arg2547_Ser2549del) variant involves the inframe deletion of 9 nucleotides located in the PIK-related kinase domain (IPR014009) (InterPro). One in silico tool predicts a damaging outcome for this variant. Functional studies confirmed that there is no detectable ATM kinase activity associated with this variant and that LCLs with this variant exhibited p53, p21, and MDM2 response that was indistinguishable from classical A-T (Stewart_2001). This variant was found in 5/246251 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528). This variant was reported in multiple AT patients (Stankovic_1998, Skowronska_2012, Stewart_2001). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This variant, c.7638_7646del, results in the deletion of 3 amino acid(s) of the ATM protein (p.Arg2547_Ser2549del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587776547, gnomAD 0.007%). This variant has been observed in individuals with breast cancer and ataxia-telangiectasia (PMID: 7792600, 8797579, 11382771, 12552559, 21787400, 22649200). This variant is also known as 7636del9 and 7638del9. ClinVar contains an entry for this variant (Variation ID: 3019). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ATM function (PMID: 11382771, 12195425, 19431188, 22649200). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 10817650]. Functional studies indicate this variant impacts protein function [PMID: 19431188].
Comment:
Observed in the heterozygous state in individuals with ATM-related cancers (Vorechovsky et al., 1996; Goldgar et al., 2011; Bunnell et al., 2017; Decker et al., 2017; Na et al., 2017; Lu et al., 2019); Published functional studies demonstrate a damaging effect: absence of kinase activity and reduced ATM protein expression (Stewart et al., 2001; Barone et al., 2009; Reiman et al., 2011); In-frame deletion of 3 amino acids in a non-repeat region predicted to critically alter the protein; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as c.7636del9 and 7638del9; This variant is associated with the following publications: (PMID: 25038946, 12552559, 21787400, 10817650, 19781682, 26556299, 32866655, 29922827, 8789452, 21792198, 9537233, 19431188, 11382771, 22649200, 21933854, 10330348, 8808599, 27276934, 8797579, 8845835, 7792600, 15279808, 12195425, 28779002, 27989354, 30128536, 34308366, 26896183, 31447099, 31948886, 32853339, 32338768, 34308104, 33804961, 23532176, 9150358, 9463314)
Comment:
This variant causes an in-frame deletion of 3 amino acids in the ATM protein. This variant is also known as 7636del9, 7637del9 and delSRI in the literature. Functional studies have reported the mutant protein to show a severely defective kinase activity (PMID: 11382771, 19431188, 21778326, 22649200). This variant has been reported in over ten heterozygous individuals affected with breast cancer (PMID: 9288106, 16652348, 21787400; Color internal data) and pancreatic cancer (PMID: 33439686; Color internal data). This variant has been observed in homozygous and compound heterozygous states in over a dozen individuals affected with autosomal recessive ataxia-telangiectasia, indicating that this variant contributes to disease (PMID: 7792600, 8755918, 8845835, 8808599, 9443866, 9463314, 10817650). This variant is reported to be a founder mutation in individuals of Irish and British ancestry (PMID: 9443866, 9463314). This variant has been identified in 7/251148 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The c.7638_7646delTAGAATTTC pathogenic mutation (also known as p.R2547_S2549del), located in coding exon 51 of the ATM gene, results from an in-frame deletion of 9 nucleotides between positions 7638 and 7646. This results in the deletion of 3 amino acids between codons 2547 and 2549. This pathogenic mutation has been reported in individuals diagnosed with breast cancer, some of whom also had family histories of other cancers (Vorechovsky I et al. Cancer Res. 1996 Sep;56:4130-3; Goldgar DE et al. Breast Cancer Res. 2011 Jul;13:R73). In addition, this mutation has been reported in a homozygous state and in conjunction with other deleterious ATM mutations in multiple individuals and/or families with ataxia-telagiectasia (Gilad S et al. Hum. Mol. Genet. 1996 Apr;5:433-9; Wright J et al. Am. J. Hum. Genet. 1996 Oct;59:839-46; Watters D et al. Oncogene. 1997 Apr;14:1911-21; Telatar M et al. Am. J. Hum. Genet. 1998 Jan;62:86-97; Stankovic T et al. Am. J. Hum. Genet. 1998 Feb;62:334-45; Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7; Buzin C et al. Hum. Mutat. 2003 Feb;21:123-31). Further, functional analysis has shown that this mutation results in intact ATM protein expression but no kinase activity (Stewart GS et al. J. Biol. Chem. 2001 Aug;276:30133-41). Of note, this alteration is also designated as 7636del9, 2546delSRI, 7638del9 and 7638_7646del9 in published literature. Based on the available evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
The ATM c.7638_7646del9 variant is predicted to result in an in-frame deletion (p.Arg2547_Ser2549del). This variant is also known in the literature as c.7636del9. This variant has been reported in patients with ataxia telangiectasia (Savitsky et al. 1995. PubMed ID: 7792600), prostate cancer (Supplemental Table 1 in Na et al. 2017. PubMed ID: 27989354), and breast cancer (Vorechovský et al. 1996. PubMed ID: 8797579; Chen et al. 1998. PubMed ID: 9537233; Lu et al. 2019. PubMed ID: 30128536, eTable 12; Goldgar et al. 2011. PubMed ID: 21787400). In vitro functional analysis showed that this variant had no kinase activity (Barone et al. 2009. PubMed ID: 19431188). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD and is interpreted as likely pathogenic/pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3019/). This variant is interpreted as pathogenic.
Comment:
Found in a male patient having exome sequencing for an unrelated indication. No known personal or family history of breast cancer.
Comment:
The ATM p.Arg2547_Ser2549del variant was identified in 14 of 6042 proband chromosomes (frequency: 0.002) from individuals or families with Ataxia-telangiectasia and breast cancer (Buzin 2003, Goldgar 2011, Li 2000, Reiman 2011). The variant was also identified in the following databases: dbSNP (ID: rs587776547) as "With Pathogenic allele", ClinVar (9x pathogenic, 1x uncertain significance), Clinvitae (5x pathogenic, 1x uncertain significance), Cosmic (1x, haematopoietic and lymphoid tumour), and the LOVD 3.0 (27x). The variant was not identified in the MutDB database. The variant was not identified in the control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). Multiple functional studies have shown the ATM protein lacks kinase activity and is expressed at low levels, confirming the pathogenicity of this variant (Barone 2009, Reiman 2011). This variant is an in-frame deletion resulting in the removal of three residues, from codon 2547 to 2549. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
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. |
Comment:
This c.7638_7646del (p.Arg2547_Ser2549del) has previously been reported in compound heterozygous and homozygous patients with ataxia telangiectasia [PMID 8808599]. Functional assays showed that the variant does not affect the level of ATM protein but does reduce the level of kinase activity [PMID 19431188]. A mouse model carrying this deletion has an increase susceptibility to develop tumors [reported as 7636del9 in PMID 12195425]. This variant was further detected in 12 out of 294 families with breast cancer. However, the difference in tumor incidence between carrier and non carrier was not statistically significant. However, this variant was detected in another patient with breast cancer [PMID 8797579]. This c.7638_7646del (p.Arg2547_Ser2549del) variant has not been observed the ExAC population database and has been observed in one individual in our internal database. It is thus interpreted as a likely pathogenic variant.
Comment:
Variant summary: The ATM c.7638_7646delTAGAATTTC (p.Arg2547_Ser2549del) variant involves the inframe deletion of 9 nucleotides located in the PIK-related kinase domain (IPR014009) (InterPro). One in silico tool predicts a damaging outcome for this variant. Functional studies confirmed that there is no detectable ATM kinase activity associated with this variant and that LCLs with this variant exhibited p53, p21, and MDM2 response that was indistinguishable from classical A-T (Stewart_2001). This variant was found in 5/246251 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528). This variant was reported in multiple AT patients (Stankovic_1998, Skowronska_2012, Stewart_2001). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Comment:
This variant, c.7638_7646del, results in the deletion of 3 amino acid(s) of the ATM protein (p.Arg2547_Ser2549del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs587776547, gnomAD 0.007%). This variant has been observed in individuals with breast cancer and ataxia-telangiectasia (PMID: 7792600, 8797579, 11382771, 12552559, 21787400, 22649200). This variant is also known as 7636del9 and 7638del9. ClinVar contains an entry for this variant (Variation ID: 3019). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ATM function (PMID: 11382771, 12195425, 19431188, 22649200). For these reasons, this variant has been classified as Pathogenic.
Comment:
This variant is considered likely pathogenic. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 10817650]. Functional studies indicate this variant impacts protein function [PMID: 19431188].
Comment:
Observed in the heterozygous state in individuals with ATM-related cancers (Vorechovsky et al., 1996; Goldgar et al., 2011; Bunnell et al., 2017; Decker et al., 2017; Na et al., 2017; Lu et al., 2019); Published functional studies demonstrate a damaging effect: absence of kinase activity and reduced ATM protein expression (Stewart et al., 2001; Barone et al., 2009; Reiman et al., 2011); In-frame deletion of 3 amino acids in a non-repeat region predicted to critically alter the protein; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as c.7636del9 and 7638del9; This variant is associated with the following publications: (PMID: 25038946, 12552559, 21787400, 10817650, 19781682, 26556299, 32866655, 29922827, 8789452, 21792198, 9537233, 19431188, 11382771, 22649200, 21933854, 10330348, 8808599, 27276934, 8797579, 8845835, 7792600, 15279808, 12195425, 28779002, 27989354, 30128536, 34308366, 26896183, 31447099, 31948886, 32853339, 32338768, 34308104, 33804961, 23532176, 9150358, 9463314)
Comment:
This variant causes an in-frame deletion of 3 amino acids in the ATM protein. This variant is also known as 7636del9, 7637del9 and delSRI in the literature. Functional studies have reported the mutant protein to show a severely defective kinase activity (PMID: 11382771, 19431188, 21778326, 22649200). This variant has been reported in over ten heterozygous individuals affected with breast cancer (PMID: 9288106, 16652348, 21787400; Color internal data) and pancreatic cancer (PMID: 33439686; Color internal data). This variant has been observed in homozygous and compound heterozygous states in over a dozen individuals affected with autosomal recessive ataxia-telangiectasia, indicating that this variant contributes to disease (PMID: 7792600, 8755918, 8845835, 8808599, 9443866, 9463314, 10817650). This variant is reported to be a founder mutation in individuals of Irish and British ancestry (PMID: 9443866, 9463314). This variant has been identified in 7/251148 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The c.7638_7646delTAGAATTTC pathogenic mutation (also known as p.R2547_S2549del), located in coding exon 51 of the ATM gene, results from an in-frame deletion of 9 nucleotides between positions 7638 and 7646. This results in the deletion of 3 amino acids between codons 2547 and 2549. This pathogenic mutation has been reported in individuals diagnosed with breast cancer, some of whom also had family histories of other cancers (Vorechovsky I et al. Cancer Res. 1996 Sep;56:4130-3; Goldgar DE et al. Breast Cancer Res. 2011 Jul;13:R73). In addition, this mutation has been reported in a homozygous state and in conjunction with other deleterious ATM mutations in multiple individuals and/or families with ataxia-telagiectasia (Gilad S et al. Hum. Mol. Genet. 1996 Apr;5:433-9; Wright J et al. Am. J. Hum. Genet. 1996 Oct;59:839-46; Watters D et al. Oncogene. 1997 Apr;14:1911-21; Telatar M et al. Am. J. Hum. Genet. 1998 Jan;62:86-97; Stankovic T et al. Am. J. Hum. Genet. 1998 Feb;62:334-45; Li A and Swift M. Am. J. Med. Genet. 2000 May;92:170-7; Buzin C et al. Hum. Mutat. 2003 Feb;21:123-31). Further, functional analysis has shown that this mutation results in intact ATM protein expression but no kinase activity (Stewart GS et al. J. Biol. Chem. 2001 Aug;276:30133-41). Of note, this alteration is also designated as 7636del9, 2546delSRI, 7638del9 and 7638_7646del9 in published literature. Based on the available evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
The ATM c.7638_7646del9 variant is predicted to result in an in-frame deletion (p.Arg2547_Ser2549del). This variant is also known in the literature as c.7636del9. This variant has been reported in patients with ataxia telangiectasia (Savitsky et al. 1995. PubMed ID: 7792600), prostate cancer (Supplemental Table 1 in Na et al. 2017. PubMed ID: 27989354), and breast cancer (Vorechovský et al. 1996. PubMed ID: 8797579; Chen et al. 1998. PubMed ID: 9537233; Lu et al. 2019. PubMed ID: 30128536, eTable 12; Goldgar et al. 2011. PubMed ID: 21787400). In vitro functional analysis showed that this variant had no kinase activity (Barone et al. 2009. PubMed ID: 19431188). This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD and is interpreted as likely pathogenic/pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/3019/). This variant is interpreted as pathogenic.
Comment:
Found in a male patient having exome sequencing for an unrelated indication. No known personal or family history of breast cancer.
Comment:
The ATM p.Arg2547_Ser2549del variant was identified in 14 of 6042 proband chromosomes (frequency: 0.002) from individuals or families with Ataxia-telangiectasia and breast cancer (Buzin 2003, Goldgar 2011, Li 2000, Reiman 2011). The variant was also identified in the following databases: dbSNP (ID: rs587776547) as "With Pathogenic allele", ClinVar (9x pathogenic, 1x uncertain significance), Clinvitae (5x pathogenic, 1x uncertain significance), Cosmic (1x, haematopoietic and lymphoid tumour), and the LOVD 3.0 (27x). The variant was not identified in the MutDB database. The variant was not identified in the control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). Multiple functional studies have shown the ATM protein lacks kinase activity and is expressed at low levels, confirming the pathogenicity of this variant (Barone 2009, Reiman 2011). This variant is an in-frame deletion resulting in the removal of three residues, from codon 2547 to 2549. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Ataxia-Telangiectasia. | Adam MP | - | 2023 | PMID: 20301790 |
| Implementing Systematic Genetic Counseling and Multigene Germline Testing for Individuals With Pancreatic Cancer. | Chittenden A | JCO oncology practice | 2021 | PMID: 33439686 |
| Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer. | Darst BF | Journal of the National Cancer Institute | 2021 | PMID: 32853339 |
| Rare germline genetic variants and risk of aggressive prostate cancer. | Nguyen-Dumont T | International journal of cancer | 2020 | PMID: 32338768 |
| Rare Germline Pathogenic Mutations of DNA Repair Genes Are Most Strongly Associated with Grade Group 5 Prostate Cancer. | Wu Y | European urology oncology | 2020 | PMID: 31948886 |
| Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. | eMERGE Consortium. Electronic address: agibbs@bcm.edu | American journal of human genetics | 2019 | PMID: 31447099 |
| Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. | Mandelker D | JAMA | 2017 | PMID: 28873162 |
| Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death. | Na R | European urology | 2017 | PMID: 27989354 |
| Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. | Schrader KA | JAMA oncology | 2016 | PMID: 26556299 |
| 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 |
| Classical ataxia telangiectasia patients have a congenitally aged immune system with high expression of CD95. | Carney EF | Journal of immunology (Baltimore, Md. : 1950) | 2012 | PMID: 22649200 |
| ATM germline heterozygosity does not play a role in chronic lymphocytic leukemia initiation but influences rapid disease progression through loss of the remaining ATM allele. | Skowronska A | Haematologica | 2012 | PMID: 21933854 |
| Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours. | Reiman A | British journal of cancer | 2011 | PMID: 21792198 |
| Rare variants in the ATM gene and risk of breast cancer. | Goldgar DE | Breast cancer research : BCR | 2011 | PMID: 21787400 |
| Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of specific DNA double-strand break-repair signaling pathways. | Keimling M | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2011 | PMID: 21778326 |
| Modeling ATM mutant proteins from missense changes confirms retained kinase activity. | Barone G | Human mutation | 2009 | PMID: 19431188 |
| The ATM missense mutation p.Ser49Cys (c.146C>G) and the risk of breast cancer. | Stredrick DL | Human mutation | 2006 | PMID: 16652348 |
| Comprehensive scanning of the ATM gene with DOVAM-S. | Buzin CH | Human mutation | 2003 | PMID: 12552559 |
| Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. | Spring K | Nature genetics | 2002 | PMID: 12195425 |
| Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer. | Scott SP | Proceedings of the National Academy of Sciences of the United States of America | 2002 | PMID: 11805335 |
| Residual ataxia telangiectasia mutated protein function in cells from ataxia telangiectasia patients, with 5762ins137 and 7271T-->G mutations, showing a less severe phenotype. | Stewart GS | The Journal of biological chemistry | 2001 | PMID: 11382771 |
| Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients. | Li A | American journal of medical genetics | 2000 | PMID: 10817650 |
| The role of ataxia-telangiectasia heterozygotes in familial breast cancer. | Chen J | Cancer research | 1998 | PMID: 9537233 |
| ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. | Stankovic T | American journal of human genetics | 1998 | PMID: 9463314 |
| Ataxia-telangiectasia: identification and detection of founder-effect mutations in the ATM gene in ethnic populations. | Telatar M | American journal of human genetics | 1998 | PMID: 9443866 |
| Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia. | Vorechovský I | Nature genetics | 1997 | PMID: 9288106 |
| Cellular localisation of the ataxia-telangiectasia (ATM) gene product and discrimination between mutated and normal forms. | Watters D | Oncogene | 1997 | PMID: 9150358 |
| A gene transcribed from the bidirectional ATM promoter coding for a serine rich protein: amino acid sequence, structure and expression studies. | Byrd PJ | Human molecular genetics | 1996 | PMID: 8923007 |
| Predominance of null mutations in ataxia-telangiectasia. | Gilad S | Human molecular genetics | 1996 | PMID: 8845835 |
| A high frequency of distinct ATM gene mutations in ataxia-telangiectasia. | Wright J | American journal of human genetics | 1996 | PMID: 8808599 |
| ATM mutations in cancer families. | Vorechovský I | Cancer research | 1996 | PMID: 8797579 |
| Mutations associated with variant phenotypes in ataxia-telangiectasia. | McConville CM | American journal of human genetics | 1996 | PMID: 8755918 |
| A single ataxia telangiectasia gene with a product similar to PI-3 kinase. | Savitsky K | Science (New York, N.Y.) | 1995 | PMID: 7792600 |
| Gene dosage and complementation analysis of ataxia telangiectasia lymphoblastoid cell lines assayed by induced chromosome aberrations. | Chen P | Mutation research | 1984 | PMID: 6504056 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ATM | - | - | - | - |
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Text-mined citations for rs587776547 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 03, 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.
NCBI staff reviewed the sequence information reported in PubMed 7792600 Fig. 2 to determine the location of this allele on the current reference sequence.