ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.5932G>T (p.Glu1978Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000051.4(ATM):c.5932G>T (p.Glu1978Ter)
Variation ID: 127414 Accession: VCV000127414.81
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11q22.3 11: 108312424 (GRCh38) [ NCBI UCSC ] 11: 108183151 (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 Jan 31, 2016 Oct 26, 2024 May 1, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000051.4:c.5932G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Glu1978Ter nonsense NM_001330368.2:c.641-3353C>A intron variant NM_001351110.2:c.*39-3353C>A intron variant NM_001351834.2:c.5932G>T NP_001338763.1:p.Glu1978Ter nonsense NC_000011.10:g.108312424G>T NC_000011.9:g.108183151G>T NG_009830.1:g.94593G>T NG_054724.1:g.162409C>A LRG_135:g.94593G>T LRG_135t1:c.5932G>T LRG_135p1:p.Glu1978Ter - Protein change
- E1978*
- Other names
-
p.E1978*:GAA>TAA
- Canonical SPDI
- NC_000011.10:108312423:G:T
-
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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00007
The Genome Aggregation Database (gnomAD) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00004
- Links
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 (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 26, 2024 | RCV000115219.22 | |
Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000205725.30 | |
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
May 1, 2024 | RCV000212035.43 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Mar 22, 2023 | RCV000515323.13 | |
Pathogenic (2) |
criteria provided, single submitter
|
Jun 11, 2020 | RCV001270929.11 | |
Pathogenic (7) |
criteria provided, multiple submitters, no conflicts
|
Feb 7, 2024 | RCV001310112.18 | |
Pathogenic (1) |
criteria provided, single submitter
|
Dec 19, 2019 | RCV001258122.9 | |
ATM-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Jan 24, 2024 | RCV004549559.2 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(Jan 09, 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: SCV000537636.4
First in ClinVar: Mar 24, 2017 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 40 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in … (more)
This variant changes 1 nucleotide in exon 40 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has shown significant association with breast cancer in meta-analyses of multiple case-control studies (OR: 5.6, 95% CI: 1.3-21.4, p=0.01; PMID: 18807267) (OR: 4.56, 95% CI: 1.35-15.42, p=0.015; PMID: 21514219). This variant is a common cause of autosomal recessive ataxia-telangiectasia in Eastern Europe (PMID: 10330348, 15880721, 16266405). This variant has been identified in 11/251182 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
Pathogenic
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000260557.11
First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu1978*) in the ATM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu1978*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is present in population databases (rs587779852, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia and breast cancer (PMID: 15880721, 16266405, 17124347, 18497957, 18807267, 19691550, 25614872). ClinVar contains an entry for this variant (Variation ID: 127414). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Jan 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000172771.9
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.E1978* mutation (also known as c.5932G>T), located in coding exon 39 of the ATM gene, results from a G to T substitution at nucleotide … (more)
The p.E1978* mutation (also known as c.5932G>T), located in coding exon 39 of the ATM gene, results from a G to T substitution at nucleotide position 5932. This changes the amino acid from a glutamate to a stop codon within exon 40. This alteration has been reported in multiple individuals with ataxia-telangiectasia from various ethnic backgrounds and is likely a Russian founder mutation (Li A et al. Am. J. Med. Genet. 2000 May;92(3):170-7; Birrell GW et al. Hum. Mutat. 2005 Jun;25(6):593; Mitui M et al. Ann. Hum. Genet. 2005 Nov;69(Pt 6):657-64; Podralska MJ et al. Mol. Genet. Genomic Med. 2014 Nov;2(6):504-11). In addition, p.E1978* has been described as a breast cancer susceptibility allele of Eastern European origin (Bogdanova N et al. Breast Cancer Res. Treat. 2009 Nov;118(1):207-11). It was also seen in a patient with prostate cancer with a Gleason score of 9 (Pritchard CC et al. N. Engl. J. Med. 2016 Aug;375(5):443-53) and in cohorts of pancreatic cancer patients (Chaffee KG et al. Genet Med. 2018 01;20:119-127; Hu C et al. Cancer Epidemiol Biomarkers Prev. 2016 Jan;25:207-11). This mutation was shown to cause skipping of coding exon 39 (reported as exon 42), as well as a premature truncation in a subset of ATM transcripts (Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun;64(6):1617-31). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by aberrant splicing, premature protein truncation, or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Pathogenic
(Dec 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Susceptibility to breast cancer
Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV001434995.1
First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020 |
Comment:
This c.5932G>T (p.Glu1978Ter) variant in exon 41 of the ATM gene creates a premature translational stop signal and is predicted to result in loss of … (more)
This c.5932G>T (p.Glu1978Ter) variant in exon 41 of the ATM gene creates a premature translational stop signal and is predicted to result in loss of function through nonsense-mediated mRNA decay or by producing a truncated protein. This variant is present in population databases (rs587779852, gnomAD 0.004379%). This variant has been reported in several individuals affected with ataxia-telangiectasia (PMID: 15880721, 16266405, 17124347, 18497957, 19691550, 25614872) and breast cancer (PMID: 18807267). It has been found to be a prevalent ATM mutation in Eastern Europe (PMID: 15880721, 16266405, 18807267). Experimental studies indicate that this nonsense change leads to out-of-frame skipping of exon 41 (PMID: 10330348, 24451234). Therefore, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Oct 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447589.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cerebellar ataxia (present)
Sex: female
|
|
Pathogenic
(Apr 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Department of Molecular Diagnostics, Institute of Oncology Ljubljana
Accession: SCV001499652.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
|
|
Pathogenic
(Jun 11, 2020)
|
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: SCV002042692.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
|
|
Pathogenic
(Feb 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000149128.17
First in ClinVar: May 17, 2014 Last updated: Mar 04, 2023 |
Comment:
Predicted to result in protein truncation or nonsense mediated decay, either by premature stop or splice defect, in a gene for which loss-of-function is a … (more)
Predicted to result in protein truncation or nonsense mediated decay, either by premature stop or splice defect, in a gene for which loss-of-function is a known mechanism of disease (Telatar 1998, Teraoka 1999, Mitui 2005, Mort 2014); Observed in the heterozygous state in individuals with ATM-related cancers (Soukupova 2008, Huang 2015, Hu 2016, Pritchard 2016, Yang 2016, Decker 2017, Brand 2018, Isaacsson Velho 2018, Penkert 2018); Case control studies suggest this variant is associated with breast cancer (Bogdanova 2009, Zhang 2011); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26483394, 26681312, 21514219, 24451234, 10817650, 16266405, 9872980, 8808599, 10330348, 19781682, 9443866, 18807267, 18497957, 26380989, 26506520, 25525159, 27112364, 10980530, 27449771, 27433846, 28779002, 29368341, 29625052, 30322717, 30113427, 30549301, 30067863, 30086788, 34426522, 32295079, 15880721, 33077847, 31589614, 33436325, 33726816, 32441320, 27535533) (less)
|
|
Pathogenic
(Feb 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: yes
Allele origin:
unknown
|
3billion
Accession: SCV003841686.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). This variant was predicted to result in … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000127414 / PMID: 9443866). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Cerebellar ataxia (present)
|
|
Pathogenic
(Apr 08, 2022)
|
criteria provided, single submitter
Method: case-control
|
Ataxia-telangiectasia syndrome
Affected status: yes
Allele origin:
germline
|
Cancer Variant Interpretation Group UK, Institute of Cancer Research, London
Accession: SCV003933670.1
First in ClinVar: Jul 01, 2023 Last updated: Jul 01, 2023 |
Comment:
Data included in classification: Truncating nonsense variant with frameshift (https://doi.org/10.1007/s10549-008-0189-9) (PVS1_vstr) Bogdanova et al 2008 (https://doi.org/10.1007/s10549-008-0189-9) Mantel–Haenszel Odds Ratio (OR): 5.6, 95% CI: 1.3–21.4, P … (more)
Data included in classification: Truncating nonsense variant with frameshift (https://doi.org/10.1007/s10549-008-0189-9) (PVS1_vstr) Bogdanova et al 2008 (https://doi.org/10.1007/s10549-008-0189-9) Mantel–Haenszel Odds Ratio (OR): 5.6, 95% CI: 1.3–21.4, P = 0.01 - p ≤0.05 and OR is above 2 (PS4_str) Termination at a codon prior to p.Arg3047 (PM5_sup) Identified in 8/32 alleles in probands with ataxia telangiectasia (https://doi.org/10.1002/humu.9341) Observations in multiple ataxia telangiectasia cases (PMID: 15880721, 16266405, 17124347, 18807267, 19691550, 25614872, 18497957) (PM3_vstr) Data not included in classification: Multiple classification as pathogenic in ClinVar Allele frequency in Non-Finnish Europeans (NFE), gnomAD v2.1 Jan 2019: 5/102582 (0.005%). Variant frequency is at a frequency of ≥0.001%. (less)
Number of individuals with the variant: 20
Clinical Features:
Breast carcinoma (present)
Comment on evidence:
Observed in 20/6412 breast cancer cases and 2/3608 controls
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002010802.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV004027248.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
Pathogenic
(May 10, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002022488.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
Pathogenic
(Feb 01, 2024)
|
criteria provided, single submitter
Method: curation
|
Ataxia-telangiectasia syndrome
Affected status: no
Allele origin:
germline
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV005052016.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Feb 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004208790.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
Pathogenic
(Jan 15, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199613.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
Pathogenic
(Jul 14, 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: SCV000694312.1
First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017 |
Comment:
Variant summary: The ATM c.5932G>T (p.Glu1978X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein due to nonsense … (more)
Variant summary: The ATM c.5932G>T (p.Glu1978X) variant results in a premature termination codon, predicted to cause a truncated or absent ATM protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., c.7327C>T [p.Arg2443X], c.7517_7520delGAGA [p.Arg2506fsX3], and c.7913G>A [p.Trp2638X]). One in silico tool predicts a damaging outcome for this variant. This variant was found in the control database ExAC and control cohorts reported in the literature at a frequency of 0.0000779 (10/128320 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic ATM variant (0.0039528). The variant has been found in homozygosity and compound heterozygosity in numerous patients and families with ataxia-telangiectasia (Podralska_MGGM_2014; Birrell_HM_2005). Additionally, a large case-control study showed that the variant is enriched in heterozygous breast cancer patients in Eastern European populations (Odds Ratio = 5.6; 95% CI = 1.323.4; p = 0.01; Bogdanova_BCRT_2009). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic for both ataxia-telangiectasia and hereditary cancer. Taken together, this variant is classified as pathogenic. (less)
|
|
Pathogenic
(Oct 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002064361.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the ATM gene demonstrated a sequence change, c.5932G>T, in exon 40 that results in the creation of a premature stop codon … (more)
DNA sequence analysis of the ATM gene demonstrated a sequence change, c.5932G>T, in exon 40 that results in the creation of a premature stop codon at amino acid position 1978, p.Glu1978*. This variant is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated ATM protein with potentially abnormal function. The p.Glu1978* change has been described in the gnomAD database with a frequency of 0.009% in the European sub-population (dbSNP rs587779852) and is a prevalent ATM variant in the Eastern European population (PMIDs: 15880721, 16266405, 18807267). This sequence change has been described in several individuals with ataxia-telangiectasia and breast cancer (PMIDs: 26380989, 30549301, 15880721, 16266405, 25614872, 17124347, 19691550, 18807267, 28779002, 30086788). The p.Glu1978* change has also been observed in individuals with pancreatic cancer, ovarian cancer, gastric cancer, and prostate cancer (PMIDs: 30067863, 27449771, 30322717, 26506520, 29368341). Functional studies have demonstrated skipping of exon 40 in the presence of this sequence change (PMIDs: 9443866, 10330348, 24451234). These collective evidences indicate that this is a pathogenic sequence change. (less)
|
|
Pathogenic
(Mar 11, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000485199.2
First in ClinVar: Jan 31, 2016 Last updated: Dec 24, 2022 |
|
|
Pathogenic
(May 10, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000611165.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
|
|
Pathogenic
(Dec 09, 2022)
|
criteria provided, single submitter
Method: research
|
Familial cancer of breast
Affected status: no
Allele origin:
germline
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV002762777.2
First in ClinVar: Dec 17, 2022 Last updated: Feb 25, 2023 |
Comment:
PVS1, PS3_MOD, PM3_VSTR
|
|
Pathogenic
(Apr 20, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV003807006.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
ACMG classification criteria: PVS1 very strong, PS3 supporting, PS4 strong, PM2 moderated, PM3 moderated
Number of individuals with the variant: 1
Clinical Features:
Breast carcinoma (present)
Geographic origin: Brazil
Method: Paired-end whole-genome sequencing
|
|
Pathogenic
(Dec 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175649.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
|
|
Pathogenic
(Jan 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV004931115.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
|
|
Pathogenic
(May 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246111.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
ATM: PVS1, PM2, PS4:Moderate, PS3:Supporting
Number of individuals with the variant: 10
|
|
Pathogenic
(Mar 22, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ataxia-telangiectasia syndrome
Familial cancer of breast
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
maternal
|
Institute of Immunology and Genetics Kaiserslautern
Accession: SCV005382120.1
First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024 |
Comment:
ACMG Criteria: PVS1, PS3, PS4, PP5; Variant was found in heterozygous state.
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001457398.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
Pathogenic
(Jan 24, 2024)
|
no assertion criteria provided
Method: clinical testing
|
ATM-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805589.3
First in ClinVar: Sep 13, 2018 Last updated: Oct 08, 2024 |
Comment:
The ATM c.5932G>T variant is predicted to result in premature protein termination (p.Glu1978*). This variant has previously been reported by several studies in individuals with … (more)
The ATM c.5932G>T variant is predicted to result in premature protein termination (p.Glu1978*). This variant has previously been reported by several studies in individuals with ataxia telangiectasia (Telatar et al 1998. PubMed ID: 9443866; Birrell et al. 2005. PubMed ID: 15880721; Mitui et al. 2005. PubMed ID: 16266405). This variant is also associated with breast cancer susceptibility (Bogdanova et al. 2009. PubMed ID: 18807267). This variant is particularly prevalent in families with a history of ataxia telangiectasia and who are of Eastern European decent (specifically Polish and Russian) (Mitui et al. 2005. PubMed ID: 16266405; Birrell et al. 2005. PubMed ID: 15880721). This variant is reported in 0.0088% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/127414/?new_evidence=true). Nonsense variants in ATM are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
Pathogenic
(Jun 11, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: yes
Allele origin:
germline
|
CZECANCA consortium
Accession: SCV001451733.1
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
|
|
Pathogenic
(Aug 26, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588922.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
|
|
not provided
(-)
|
no classification provided
Method: phenotyping only
|
Ataxia-telangiectasia syndrome
Familial cancer of breast
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: yes
Allele origin:
maternal
|
GenomeConnect - Invitae Patient Insights Network
Accession: SCV004228579.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
Variant interpreted as Pathogenic and reported on 08-07-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Pathogenic and reported on 08-07-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. (less)
Clinical Features:
Abnormal skull morphology (present) , Autoimmunity (present) , Immunodeficiency (present) , Recurrent infections (present) , Abnormality of coordination (present) , Pregnancy history (present)
Indication for testing: Diagnostic
Age: 0-9 years
Sex: female
Method: Gene Panel Sequencing
Testing laboratory: Invitae
Date variant was reported to submitter: 2019-08-07
Testing laboratory interpretation: Pathogenic
|
|
click to load more click to collapse |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history. | Chaffee KG | Genetics in medicine : official journal of the American College of Medical Genetics | 2018 | PMID: 28726808 |
Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations. | Yang XR | Human genetics | 2016 | PMID: 27449771 |
Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer. | Pritchard CC | The New England journal of medicine | 2016 | PMID: 27433846 |
Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients. | Hu C | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2016 | PMID: 26483394 |
Prevalence of deleterious ATM germline mutations in gastric cancer patients. | Huang DS | Oncotarget | 2015 | PMID: 26506520 |
Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report. | Navratil M | The American journal of case reports | 2015 | PMID: 26380989 |
Ten new ATM alterations in Polish patients with ataxia-telangiectasia. | Podralska MJ | Molecular genetics & genomic medicine | 2014 | PMID: 25614872 |
Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. | Huang Y | Neuromolecular medicine | 2013 | PMID: 23807571 |
Rare, evolutionarily unlikely missense substitutions in ATM confer increased risk of breast cancer. | Tavtigian SV | American journal of human genetics | 2009 | PMID: 19781682 |
Founder effects for ATM gene mutations in Italian Ataxia Telangiectasia families. | Chessa L | Annals of human genetics | 2009 | PMID: 19691550 |
A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer. | Bogdanova N | Breast cancer research and treatment | 2009 | PMID: 18807267 |
Contribution of mutations in ATM to breast cancer development in the Czech population. | Soukupova J | Oncology reports | 2008 | PMID: 18497957 |
DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations. | Magliozzi M | Disease markers | 2006 | PMID: 17124347 |
ATM gene founder haplotypes and associated mutations in Polish families with ataxia-telangiectasia. | Mitui M | Annals of human genetics | 2005 | PMID: 16266405 |
ATM mutations, haplotype analysis, and immunological status of Russian patients with ataxia telangiectasia. | Birrell GW | Human mutation | 2005 | PMID: 15880721 |
Characterization of ATM mutations in 41 Nordic families with ataxia telangiectasia. | Laake K | Human mutation | 2000 | PMID: 10980530 |
Mutations at the ataxia-telangiectasia locus and clinical phenotypes of A-T patients. | Li A | American journal of medical genetics | 2000 | PMID: 10817650 |
Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences. | Teraoka SN | American journal of human genetics | 1999 | PMID: 10330348 |
Characterization of ATM gene mutations in 66 ataxia telangiectasia families. | Sandoval N | Human molecular genetics | 1999 | PMID: 9887333 |
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 |
click to load more click to collapse |
Text-mined citations for rs587779852 ...
HelpRecord 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.