Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235097 | SCV000149133 | uncertain significance | not provided | 2024-03-13 | criteria provided, single submitter | clinical testing | 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: 28779002, 24356096, 27720647, 26580448, 26837699, 28873162, 29470806, 29522266, 25186627, 20305132, 33436325, 34204722, 30303537, 30306255, 28652578, 33471991, 31206626, 34250389, 36685941, 35451682, 34326862) |
Labcorp Genetics |
RCV000122868 | SCV000166126 | likely benign | Ataxia-telangiectasia syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000115224 | SCV000184444 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-05 | criteria provided, single submitter | clinical testing | The p.G204R variant (also known as c.610G>A), located in coding exon 5 of the ATM gene, results from a G to A substitution at nucleotide position 610. The glycine at codon 204 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been detected in ethnically diverse cohorts of breast, ovarian, prostate, and/or chronic lymphocytic leukemia patients, as well as healthy controls (Hauke J et al. Cancer Med. 2018 04;7:1349-1358; Singh J et al. Breast Cancer Res. Treat. 2018 Jul; Dorling et al. N Engl J Med. 2021 02;384:428-439; 170:189-196; Weitzel JN et al. Cancer, 2019 08;125:2829-2836; Karlsson Q et al. Eur Urol Oncol. 2021 08;4:570-579; Nadeu F et al. Blood. 2016 04;127:2122-30). This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with rhabdomyosarcoma (Zhang J et al. N Engl J Med. 2015 Dec;373:2336-2346). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000115224 | SCV000537552 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-16 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 204 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 20305132, 25186627, 28779002, 29470806, 29522266, 34204722), chronic lymphocytic leukemia (PMID: 26837699, 28652578), and in unaffected controls (PMID: 28652578). In a large international case-control study, this variant was reported in 9/60457 breast cancer cases and 8/53453 controls (OR=0.995, 95%CI 0.384 to 2.578, p-value=1; PMID: 33471991). This variant has also been identified in 29/282440 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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. |
Ce |
RCV000235097 | SCV000780399 | uncertain significance | not provided | 2017-12-01 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004549561 | SCV000805595 | uncertain significance | ATM-related disorder | 2024-01-29 | criteria provided, single submitter | clinical testing | The ATM c.610G>A variant is predicted to result in the amino acid substitution p.Gly204Arg. This variant has been reported in an individual with chronic lymphocytic leukemia (Supplementary Table S8, Nadeu et al. 2016. PubMed ID: 26837699) and in individuals with ATM associated hereditary cancers such as breast and/or ovarian cancer (Supplementary Table S1, Hauke et al. 2018. PubMed ID: 29522266; Supplementary Table S3, Singh et al. 2018. PubMed ID: 29470806). This variant is reported in 0.023% of alleles in individuals of Latino descent in gnomAD and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/127419/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Eurofins Ntd Llc |
RCV000235097 | SCV000861881 | uncertain significance | not provided | 2018-06-11 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000764935 | SCV000896107 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000122868 | SCV001262432 | uncertain significance | Ataxia-telangiectasia syndrome | 2017-04-28 | 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193006 | SCV001361525 | likely benign | not specified | 2022-02-24 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.610G>A (p.Gly204Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251150 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Breast Cancer (0.00011 vs 0.001), allowing no conclusion about variant significance. c.610G>A has been reported in the literature in individuals affected with breast and/or ovarian cancer, prostate cancer, chronic lymphocytic leukemia and rhabdosarcoma in settings of multigene panel testing and in unaffected control cohorts (example, Tung 2015, Decker 2017, Singh 2018, Nadeu 2016, Tiao 2017, Zhang 2015, Bonache_2018, Girard_2019, Karlsson_2021). These reports do not provide unequivocal conclusions about association of the variant with Ataxia Telangiectasia or Breast Cancer. At-least one co-occurrence with another pathogenic variant has been reported in an individual undergoing multigene panel testing for breast cancer (BRCA1 c.5172dupA, p.Glu1725Argfs*7, Tung_2015), providing supporting evidence for a benign role. A recent study that included this variant reports that carriers of loss of function variants in the ATM gene have a significantly higher risk of developing breast cancer than carriers of an ATM missense variant (OR for LOF =17.4; OR for missense = 1.6) (Girard_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten ClinVar submitters have assessed the variant since 2014: nine have classified the variant as of uncertain significance and one as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798321 | SCV002042713 | uncertain significance | Breast and/or ovarian cancer | 2022-11-23 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115224 | SCV002537089 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-23 | criteria provided, single submitter | curation | |
Institute for Biomarker Research, |
RCV000115224 | SCV004014949 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-30 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV001193006 | SCV004027139 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003335103 | SCV004043170 | likely benign | Familial cancer of breast | 2023-08-17 | 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]. |
Baylor Genetics | RCV003335103 | SCV004208374 | uncertain significance | Familial cancer of breast | 2024-03-09 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000235097 | SCV004221216 | uncertain significance | not provided | 2023-04-18 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.00023 (8/35374 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals/families with breast and/or ovarian cancer (PMIDs: 34204722 (2021), 31206626 (2019), 29470806 (2018), 29522266 (2018), 30306255 (2018), 28779002 (2017), 25186627 (2015), 20305132 (2010)), lymphocytic leukemia (PMIDs: 28652578 (2017), 26837699 (2016)), rhabdomyosarcoma (PMID: 26580448 (2015)), and prostate cancer (PMID: 33436325 (2021). The variant has also been observed in healthy controls (PMIDs: 33436325 (2021), 30303537 (2019), 31206626 (2019), 28652578 (2017), 28779002 (2017)). In an individual with breast cancer, this variant co-occurred with a pathogenic variant in the BRCA1 gene, suggesting it may not be the cause of disease (PMID: 25186627 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
Athena Diagnostics | RCV000235097 | SCV004229281 | uncertain significance | not provided | 2023-04-18 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function. |
Genome |
RCV001535620 | SCV001749645 | not provided | Ataxia-telangiectasia syndrome; Malignant tumor of breast | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 05-06-2016 by Ambry Genetics. 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. | |
Laboratory of Diagnostic Genome Analysis, |
RCV000235097 | SCV002036912 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000235097 | SCV002037469 | uncertain significance | not provided | no assertion criteria provided | clinical testing |