Total submissions: 26
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000586113 | SCV000149171 | uncertain significance | not provided | 2024-03-12 | criteria provided, single submitter | clinical testing | Observed in individuals with a personal or family history of breast or other cancers, but also in unaffected controls (PMID: 18384426, 24121791, 25186627, 27153395, 27067391, 28779002, 32522261, 33471991, 35264596); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21445571, 25503501, 18384426, 22529920, 19781682, 24121791, 26580448, 25525159, 27153395, 27067391, 25925381, 30197789, 17344846, 25186627, 28652578, 30287823, 34426522, 35312250, 36029002, 33471991, 35264596, 32522261, 28779002, 15279808, 23532176) |
Ambry Genetics | RCV000115262 | SCV000184388 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-06 | criteria provided, single submitter | clinical testing | The p.R2719H variant (also known as c.8156G>A), located in coding exon 55 of the ATM gene, results from a G to A substitution at nucleotide position 8156. The arginine at codon 2719 is replaced by histidine, an amino acid with highly similar properties. This alteration has been identified in multiple individuals with a personal and/or family history of breast cancer (Brunet J et al. Clin. Genet. 2008 May;73:465-73; Tavtigian S et al. Am. J. Hum. Genet. 2009 Oct;85:427-46; Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190; Pereira JZ et al. Mol Biol Rep, 2022 Oct;49:9509-9520; Sánchez Castro EE et al. Rev Fac Cien. Med Univ Nac Cordoba. 2022 03;79(1):53-56.). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV000232453 | SCV000283074 | uncertain significance | Ataxia-telangiectasia syndrome | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2719 of the ATM protein (p.Arg2719His). This variant is present in population databases (rs55982963, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with breast cancer (PMID: 18384426, 19781682, 21445571, 35264596). ClinVar contains an entry for this variant (Variation ID: 127456). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Color Diagnostics, |
RCV000115262 | SCV000682464 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-16 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 2719 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. The variant has been reported in individuals affected with breast cancer (PMID: 18384426, 19781682, 35312250, 33471991, 35312250), as well as in two women older than age 70 years with no personal history of cancer (FLOSSIES; https://whi.color.com/). In a large international case-control meta-analysis, this variant was reported in 22/60466 cases breast cancer cases and 11/53461 controls (OR=1.769, 95%CI 0.858 to 3.648, p-value=0.162; PMID: 33471991). This variant has also been identified in 37/250828 chromosomes in the general population by the Genome Aggregation Database (gnomAD), including 1 homozygous individual. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586113 | SCV000694372 | uncertain significance | not provided | 2017-02-16 | criteria provided, single submitter | clinical testing | Variant summary: The c.8156G>A (p.Arg2719His) in ATM gene is a missense change that involves a conserved nucleotide and 4/5 in silico tools predict deleterious outcome. The variant is located in the PI3/PI4-kinase domain, however no functional studies confirming deleterious effect of this change have been reported at the time of evaluation. The variant is present in the control population dataset of ExAC at a frequency of 0.00017 (20/116502 chrs tested), predominantly in individuals of Latino descent (0.0017; 13/1130chrs tested), including 1 homozygote. The latter frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.0010, suggesting it is may be an ethnic-specific functional polymorphism. The variant has been reported in BrC pts without strong evidence for causality. The variant is cited as VUS by a reputable databases/clinical laboratories without evidence to independently evaluate. Taking together, the variant was classified as VUS. |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000232453 | SCV000745134 | uncertain significance | Ataxia-telangiectasia syndrome | 2016-07-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000232453 | SCV000838607 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000764949 | SCV000896121 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000586113 | SCV001148447 | uncertain significance | not provided | 2024-10-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000232453 | SCV001264110 | uncertain significance | Ataxia-telangiectasia syndrome | 2017-04-27 | criteria provided, single submitter | clinical testing | 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. |
Division of Medical Genetics, |
RCV001257471 | SCV001434277 | uncertain significance | Familial cancer of breast | 2019-10-08 | criteria provided, single submitter | clinical testing | This variant has been reported in the literature in individuals with breast cancer (Brunet 2008, Tavtigian 2009, Grana 2011). This variant has an overall allele frequency of 0.0001 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). In silico analyses indicate this is an evolutionarily conserved residue. PP3 |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586113 | SCV001469960 | uncertain significance | not provided | 2024-02-06 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000586113 | SCV001475573 | uncertain significance | not provided | 2020-03-27 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000232453 | SCV001781321 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV001798327 | SCV002042975 | uncertain significance | Breast and/or ovarian cancer | 2022-11-22 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818260 | SCV002071379 | uncertain significance | not specified | 2021-02-26 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115262 | SCV002527174 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-01 | criteria provided, single submitter | curation | |
MGZ Medical Genetics Center | RCV001257471 | SCV002579417 | uncertain significance | Familial cancer of breast | 2021-09-02 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000232453 | SCV003827468 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-09-07 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV000586113 | SCV004026395 | uncertain significance | not provided | 2023-05-17 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV001257471 | SCV005083992 | likely benign | Familial cancer of breast | 2024-06-18 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
Center for Genomic Medicine, |
RCV001818260 | SCV005090404 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Clinical Genetics Laboratory, |
RCV000586113 | SCV005199623 | uncertain significance | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000232453 | SCV000734791 | uncertain significance | Ataxia-telangiectasia syndrome | no assertion criteria provided | clinical testing | ||
Natera, |
RCV000232453 | SCV001462604 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-09-16 | no assertion criteria provided | clinical testing | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000586113 | SCV001979623 | uncertain significance | not provided | no assertion criteria provided | clinical testing |