ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.2805G>C (p.Thr935=)
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.
Uncertain significance(1); Benign(7); Likely benign(10)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000051.4(ATM):c.2805G>C (p.Thr935=)
Variation ID: 135746 Accession: VCV000135746.63
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108268576 (GRCh38) [ NCBI UCSC ] 11: 108139303 (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 May 29, 2016 Oct 8, 2024 Jul 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.2805G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Thr935= synonymous NM_001351834.2:c.2805G>C NP_001338763.1:p.Thr935= synonymous NC_000011.10:g.108268576G>C NC_000011.9:g.108139303G>C NG_009830.1:g.50745G>C LRG_135:g.50745G>C LRG_135t1:c.2805G>C LRG_135p1:p.Thr935= - Protein change
- Other names
- p.T935T:ACG>ACC
- Canonical SPDI
- NC_000011.10:108268575:G:C
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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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0.00040 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00031
Trans-Omics for Precision Medicine (TOPMed) 0.00033
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00038
1000 Genomes Project 0.00040
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 | ||
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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
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. |
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ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10833 | 17429 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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. |
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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Feb 1, 2024 | RCV000122836.30 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Jun 11, 2024 | RCV000123732.12 | |
Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
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Aug 15, 2023 | RCV000211989.11 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2024 | RCV000586912.35 | |
Likely benign (1) |
no assertion criteria provided
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- | RCV001357062.4 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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May 10, 2024 | RCV003315805.4 | |
Likely benign (1) |
criteria provided, single submitter
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May 1, 2023 | RCV003149832.5 |
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. |
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Likely benign
(Apr 27, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000537452.1
First in ClinVar: May 29, 2016 Last updated: May 29, 2016 |
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Likely benign
(Apr 03, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000805527.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
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Benign
(Sep 17, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV001143102.1
First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020 |
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Uncertain significance
(Apr 27, 2017)
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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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Illumina Laboratory Services, Illumina
Accession: SCV001263807.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Likely benign
(Oct 22, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694235.3
First in ClinVar: Mar 17, 2018 Last updated: Nov 12, 2020 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000166094.15
First in ClinVar: Jun 16, 2014 Last updated: Feb 20, 2024 |
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Benign
(Oct 15, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000167075.11
First in ClinVar: Jun 23, 2014 Last updated: Jun 01, 2016 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Likely benign
(Jun 08, 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: SCV000792119.1
First in ClinVar: Aug 04, 2018 Last updated: Aug 04, 2018 |
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Likely benign
(Dec 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002068485.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Likely benign
(Sep 17, 2020)
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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: SCV002532852.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
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Benign
(Jul 07, 2023)
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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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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004017214.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
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Likely benign
(Aug 15, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002760538.3
First in ClinVar: Dec 17, 2022 Last updated: Aug 18, 2023 |
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Benign
(Jun 19, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220887.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
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Likely benign
(May 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
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CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV003838475.2
First in ClinVar: Mar 11, 2023 Last updated: Feb 04, 2024 |
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Likely benign
(Aug 19, 2014)
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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: SCV000212981.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Benign
(May 10, 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: SCV005083921.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
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Likely benign
(Jul 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002497170.17
First in ClinVar: Apr 08, 2022 Last updated: Oct 08, 2024 |
Comment:
ATM: BP4, BP7
Number of individuals with the variant: 5
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Benign
(Jun 11, 2024)
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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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Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV005205744.1
First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024 |
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Likely benign
(Apr 17, 2020)
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no assertion criteria provided
Method: clinical testing
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Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001461095.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001965942.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552395.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ATM p.Thr935= variant was identified in 4 of 5562 proband chromosomes (frequency: 0.001) from individuals or families with contralateral breast cancer, breast carcinoma or … (more)
The ATM p.Thr935= variant was identified in 4 of 5562 proband chromosomes (frequency: 0.001) from individuals or families with contralateral breast cancer, breast carcinoma or chronic lymphocytic leukemia (Bernstein 2010, Mangone 2015, Skowronska 2012, Teraoka 2001). The variant was also identified in dbSNP (ID: rs55934812) as "With Likely benign, Uncertain significance allele", ClinVar (classified as benign by GeneDx; as likely benign by Invitae, Ambry Genetics, Color Genomics; as uncertain significance by Integrated Genetics/Laboratory Corporation of America), and in LOVD 3.0 (1x as likely benign). The variant was not identified in COGR, and Cosmic databases. The variant was identified in control databases in 81 of 277128 chromosomes (1 homozygous) at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 2 of 24032 chromosomes (freq: 0.0001), Other in 5 of 6464 chromosomes (freq: 0.001), Latino in 14 of 34420 chromosomes (freq: 0.0004), and European in 60 of 126690 chromosomes (freq: 0.001); it was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Thr935= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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 the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (less)
Number of individuals with the variant: 2
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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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Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition. | Sanmartín E | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28830922 |
TIAM1 variants improve clinical outcome in neuroblastoma. | Sanmartín E | Oncotarget | 2017 | PMID: 28423360 |
ATM gene mutations in sporadic breast cancer patients from Brazil. | Mangone FR | SpringerPlus | 2015 | PMID: 25625042 |
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 |
Radiation exposure, the ATM Gene, and contralateral breast cancer in the women's environmental cancer and radiation epidemiology study. | Bernstein JL | Journal of the National Cancer Institute | 2010 | PMID: 20305132 |
Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma. | Fang NY | Proceedings of the National Academy of Sciences of the United States of America | 2003 | PMID: 12697903 |
Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history. | Teraoka SN | Cancer | 2001 | PMID: 11505391 |
Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia. | Stankovic T | Lancet (London, England) | 1999 | PMID: 10023947 |
Text-mined citations for rs55934812 ...
HelpRecord last updated Oct 08, 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.