ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.7789-3T>G
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.7789-3T>G
Variation ID: 219629 Accession: VCV000219629.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108332759 (GRCh38) [ NCBI UCSC ] 11: 108203486 (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 Feb 19, 2018 Aug 25, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.7789-3T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_001330368.2:c.641-23688A>C intron variant NM_001351110.2:c.*38+2461A>C intron variant NM_001351834.2:c.7789-3T>G intron variant NC_000011.10:g.108332759T>G NC_000011.9:g.108203486T>G NG_009830.1:g.114928T>G NG_054724.1:g.142074A>C LRG_135:g.114928T>G LRG_135t1:c.7789-3T>G - Protein change
- Other names
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- Canonical SPDI
- NC_000011.10:108332758:T:G
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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.
The Genome Aggregation Database (gnomAD), exomes 0.00000
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
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10820 | 17411 | |
C11orf65 | - | - | - |
GRCh38 GRCh37 |
3 | 6573 |
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
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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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Nov 9, 2023 | RCV000206828.21 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 23, 2023 | RCV000562166.17 | |
Likely pathogenic (1) |
no assertion criteria provided
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Jun 11, 2019 | RCV001270955.9 | |
Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV001310118.11 | |
Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 9, 2024 | RCV003326373.14 |
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
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Apr 21, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000791081.1
First in ClinVar: May 26, 2018 Last updated: May 26, 2018 |
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Pathogenic
(Apr 02, 2020)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: yes
Allele origin:
germline
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Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499660.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(Jul 02, 2018)
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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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Mendelics
Accession: SCV000838597.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Pathogenic
(May 23, 2023)
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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: SCV000682436.3
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant causes a T to G nucleotide substitution at the -3 position of intron 52 of the ATM gene. Functional RNA studies have shown … (more)
This variant causes a T to G nucleotide substitution at the -3 position of intron 52 of the ATM gene. Functional RNA studies have shown that this variant causes out-of-frame skipping of exon 53 (referred to as exon 55 in the literature) resulting in a frameshift and premature truncation (PMID: 8808599). This variant has been reported in the homozygous state and in the compound heterozygous state in individuals affected with ataxia-telangiectasia (PMID: 8808599, 12815592, 17124347, 21965147). This variant has also been detected in a cohort of individuals affected with breast cancer (PMID: 35264596). This variant has been identified in 1/249636 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)
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Pathogenic
(Nov 09, 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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Invitae
Accession: SCV000259612.10
First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024 |
Comment:
This sequence change falls in intron 52 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. … (more)
This sequence change falls in intron 52 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with ataxia-telangiectasia (PMID: 8808599, 12815592, 17124347, 21965147). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 219629). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 53 (also known as exon 55) and introduces a premature termination codon (PMID: 8808599). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jun 28, 2022)
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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: SCV000665478.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The c.7789-3T>G intronic variant results from a T to G substitution 3 nucleotides upstream from coding exon 52 in the ATM gene. This alteration has … (more)
The c.7789-3T>G intronic variant results from a T to G substitution 3 nucleotides upstream from coding exon 52 in the ATM gene. This alteration has been reported in conjunction with a second ATM alteration in multiple patients with ataxia-telangiectasia (Wright J et al. Am. J. Hum. Genet. 1996 Oct; 59(4):839-46; Mitui M et al. Hum. Mutat. 2003 Jul; 22(1):43-50; Coutinho G et al. Am. J. Med. Genet. A 2004 Apr; 126A(1):33-40; Magliozzi M et al. Dis. Markers 2006; 22(4):257-64; Demuth I et al. Neurogenetics 2011 Nov; 12(4):273-82). In one study, this alteration was found to result in alternatively spliced cDNA due to skipping of coding exon 53 (Wright J et al. Am. J. Hum. Genet. 1996 Oct;59(4):839-46). Of note, this alteration is also designated as IVS54-3T>G in published literature. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Feb 09, 2022)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002538204.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The ATM c.7789-3T>G variant has been reported as homozygous in one individual and as compound heterozygous in at least three individuals with ataxia telangiectasia (PMID: … (more)
The ATM c.7789-3T>G variant has been reported as homozygous in one individual and as compound heterozygous in at least three individuals with ataxia telangiectasia (PMID: 12815592, 15039971, 17124347, 21965147, 8808599), consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as IVS54-3T>G in literature. Experimental studies have shown that this variant results in the skipping of exon 53 (also known as exon 55) (PMID: 8808599) and may result in an absent or disrupted protein product. This variant was observed in 1/113000 chromosomes in the Non-Finnish European population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID: 219629). Based on the current evidence available, this variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 28, 2021)
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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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Baylor Genetics
Accession: SCV004216244.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Feb 01, 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: SCV004932246.1
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: 8808599, 12815592, 17124347, 21965147].
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Likely pathogenic
(Aug 01, 2023)
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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: SCV004033162.9
First in ClinVar: Sep 16, 2023 Last updated: Aug 04, 2024 |
Comment:
ATM: PM3:Strong, PM2, PP3
Number of individuals with the variant: 1
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Likely pathogenic
(Jan 09, 2024)
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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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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199621.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Likely pathogenic
(Jun 11, 2019)
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no assertion criteria provided
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
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CZECANCA consortium
Accession: SCV001451759.1
First in ClinVar: Dec 24, 2020 Last updated: Dec 24, 2020 |
Number of individuals with the variant: 1
Ethnicity/Population group: Slavic
Geographic origin: Czech Republic
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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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Detection of germline variants in Brazilian breast cancer patients using multigene panel testing. | Guindalini RSC | Scientific reports | 2022 | PMID: 35264596 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
New mutations in the ATM gene and clinical data of 25 AT patients. | Demuth I | Neurogenetics | 2011 | PMID: 21965147 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations. | Magliozzi M | Disease markers | 2006 | PMID: 17124347 |
Five haplotypes account for fifty-five percent of ATM mutations in Brazilian patients with ataxia telangiectasia: seven new mutations. | Coutinho G | American journal of medical genetics. Part A | 2004 | PMID: 15039971 |
Independent mutational events are rare in the ATM gene: haplotype prescreening enhances mutation detection rate. | Mitui M | Human mutation | 2003 | PMID: 12815592 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
A high frequency of distinct ATM gene mutations in ataxia-telangiectasia. | Wright J | American journal of human genetics | 1996 | PMID: 8808599 |
Text-mined citations for rs864622185 ...
HelpRecord last updated Aug 25, 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.