ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6088A>G (p.Ile2030Val) (rs145847315)

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Total submissions: 19
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122865 SCV000166123 benign Ataxia-telangiectasia syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV001573283 SCV000167096 benign not provided 2019-01-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22995991, 11746755, 11505391, 24728327, 17517479, 11849780, 25980754)
Ambry Genetics RCV000129192 SCV000183931 benign Hereditary cancer-predisposing syndrome 2014-06-30 criteria provided, single submitter clinical testing This alteration is classified as 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.
Counsyl RCV000122865 SCV000220654 likely benign Ataxia-telangiectasia syndrome 2014-08-28 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120150 SCV000230532 benign not specified 2015-01-07 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120150 SCV000246618 benign not specified 2016-11-23 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000129192 SCV000576461 likely benign Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129192 SCV000682300 benign Hereditary cancer-predisposing syndrome 2014-12-06 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120150 SCV000805592 benign not specified 2017-08-11 criteria provided, single submitter clinical testing
Mendelics RCV000122865 SCV001138535 likely benign Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000122865 SCV001157047 benign Ataxia-telangiectasia syndrome 2019-06-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000122865 SCV001263993 benign 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
ITMI RCV000120150 SCV000084291 not provided not specified 2013-09-19 no assertion provided reference population
True Health Diagnostics RCV000129192 SCV000787875 likely benign Hereditary cancer-predisposing syndrome 2017-10-26 no assertion criteria provided clinical testing
Natera, Inc. RCV000122865 SCV001457402 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357876 SCV001553470 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Ile2030Val variant was identified in 5 of 3368 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer or lynch syndrome and was present in 1 of 162 control chromosomes (Ho 2017, Iannuzzi 2002, Teraoka 2001, Yorczyk 2015, Yurgelun 2015). The variant was also identified in dbSNP (ID: rs145847315) as “With other allele”, ClinVar (as benign by Invitae, GeneDx, Ambry Genetics, EDL Genetic Diagnostics, University of Chicago, and Color Genomics, and as likely benign by Counsyl, and Institute for Biomarker Research), Clinvitae (4x), databases. The variant was not identified in Cosmic, MutDB, LOVD 3.0, or ATM-LOVD databases. The variant was identified in control databases in 444 of 277186 chromosomes (6 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 417 of 24038 chromosomes (freq: 0.02), Other in 4 of 6466 chromosomes (freq: 0.001), Latino in 19 of 34416 chromosomes (freq: 0.001), European in 4 of 126698 chromosomes (freq: 0.00003), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Ile2030 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573283 SCV001798915 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000120150 SCV001808206 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000120150 SCV001920406 benign not specified no assertion criteria provided clinical testing

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