ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.609C>T (p.Asp203=) (rs144709948)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122866 SCV000166124 benign Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx 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: 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.
PreventionGenetics,PreventionGenetics RCV000211950 SCV000301679 likely benign not specified criteria provided, single submitter clinical testing
Color Health, Inc RCV000123719 SCV000682306 benign Hereditary cancer-predisposing syndrome 2016-04-18 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000122866 SCV000745121 likely benign Ataxia-telangiectasia syndrome 2017-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000122866 SCV000793299 likely benign Ataxia-telangiectasia syndrome 2017-08-09 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679133 SCV000805594 likely benign not provided 2015-06-18 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000679133 SCV000840949 benign not provided 2019-01-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283242 SCV000885038 benign none provided 2020-03-06 criteria provided, single submitter clinical testing
Mendelics RCV000122866 SCV001138438 likely benign Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679133 SCV001148399 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina 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).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000122866 SCV000732987 likely benign Ataxia-telangiectasia syndrome no assertion criteria provided clinical testing
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,Sinai Health System 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.

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