Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000122866 | SCV000166124 | benign | Ataxia-telangiectasia syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000211950 | SCV000167062 | benign | not specified | 2014-01-20 | criteria provided, single submitter | clinical testing | 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. |
Ambry Genetics | RCV000123719 | SCV000213018 | likely benign | Hereditary cancer-predisposing syndrome | 2014-06-27 | criteria provided, single submitter | clinical testing | 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. |
Prevention |
RCV000211950 | SCV000301679 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Color Diagnostics, |
RCV000123719 | SCV000682306 | benign | Hereditary cancer-predisposing syndrome | 2016-04-18 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000122866 | SCV000793299 | likely benign | Ataxia-telangiectasia syndrome | 2017-08-09 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000679133 | SCV000840949 | benign | not provided | 2019-01-10 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000679133 | SCV000885038 | benign | not provided | 2023-09-07 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000122866 | SCV001138438 | likely benign | Ataxia-telangiectasia syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000679133 | SCV001148399 | likely benign | not provided | 2024-09-01 | criteria provided, single submitter | clinical testing | ATM: BP4, BS1 |
Illumina Laboratory Services, |
RCV000122866 | SCV001262431 | 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). 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. |
Spanish ATM Cancer Susceptibility Variant Interpretation Working Group | RCV000123719 | SCV001911471 | likely benign | Hereditary cancer-predisposing syndrome | 2020-06-17 | criteria provided, single submitter | clinical testing | The c.609C>T p.(Asp203=) variant has an allele frequency of 0.00238 (0.23%, 281/ 117988 alleles) in the Non-Finnish European population of the gnomAD v2.1.1 non-cancer dataset (BS1; http://gnomad.broadinstitute.org). It is a silent variant not predicted to lead to a splicing alteration according to SPiCE, and no splicing site is created or activated according to at least 3 splicing predictors of the set SpliceSiteFinderlike - MaxEntScan - NNSplice - GeneSplicer (BP4). The variant is located at a nucleotide that is not highly conserved across species, based on PhyloP (BP7). Therefore, this variant meets criteria to be classified as likely benign. Adapted ACMG/AMP rules applied as defined by the Spanish ATM working group: BS1 + BP4 + BP7 (PMID: 33280026). |
CHEO Genetics Diagnostic Laboratory, |
RCV001798396 | SCV002042706 | likely benign | Breast and/or ovarian cancer | 2023-04-27 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000211950 | SCV002070857 | likely benign | not specified | 2020-04-23 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000123719 | SCV002537055 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-20 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000211950 | SCV002760508 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679133 | SCV002774003 | benign | not provided | 2023-02-08 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV003315809 | SCV004017269 | benign | Familial cancer of breast | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003315809 | SCV005084014 | benign | Familial cancer of breast | 2024-04-22 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
True Health Diagnostics | RCV000123719 | SCV000787876 | likely benign | Hereditary cancer-predisposing syndrome | 2017-10-30 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000679133 | SCV001554085 | likely benign | not provided | no assertion criteria provided | clinical testing | The ATM p.Asp203= variant was not identified in the literature nor was it identified in COGR, MutDB, LOVD 3.0, or ATM-LOVD. The variant was identified in dbSNP (ID: rs144709948) as “With other allele”, in ClinVar (4x as likely benign by Ambry Genetics, PreventionGenetics, and the University Midical Center Groningen and 3x as benign by Invitae, GeneDx, and Color Genomics). The variant was also listed the Cosmic database (1x in Acute myeloid leukemia). The variant was identified in control databases in 397 of 276884 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 12 of 24010 chromosomes (freq: 0.0005), Other in 15 of 6446 chromosomes (freq: 0.002), Latino in 33 of 34358 chromosomes (freq: 0.001), European Non-Finnish in 286 of 126536 chromosomes (freq: 0.002), Ashkenazi Jewish in 5 of 10148 chromosomes (freq: 0.0005), European Finnish in 36 of 25754 chromosomes (freq: 0.001), and South Asian in 10 of 30778 chromosomes (freq: 0.0003) while the variant was not observed in the East Asian, populations. The p.Asp203= 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. |