ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2442C>A (p.Asp814Glu) (rs3218695)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000120123 SCV000167071 benign not specified 2013-12-16 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 RCV000129054 SCV000183749 benign Hereditary cancer-predisposing syndrome 2014-08-29 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.
Invitae RCV000206885 SCV000262027 benign Ataxia-telangiectasia syndrome 2020-12-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129054 SCV000682054 benign Hereditary cancer-predisposing syndrome 2020-11-30 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000206885 SCV000743723 benign Ataxia-telangiectasia syndrome 2016-02-09 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000206885 SCV000745809 benign Ataxia-telangiectasia syndrome 2017-03-24 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120123 SCV000805516 benign not specified 2017-03-30 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000206885 SCV001262550 benign 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. 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.
Athena Diagnostics Inc RCV000120123 SCV001879395 benign not specified 2020-10-15 criteria provided, single submitter clinical testing
ITMI RCV000120123 SCV000084261 not provided not specified 2013-09-19 no assertion provided reference population
Natera, Inc. RCV000206885 SCV001462069 benign Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001357064 SCV001552397 benign Malignant tumor of breast no assertion criteria provided clinical testing The ATM p.Asp814Glu variant was identified in 1 of 9370 proband chromosomes (frequency: 0.0001) from individuals or families with breast cancer and was present in 6 of 11286 control chromosomes (frequency: 0.0005) from healthy individuals (Johnson 2007, Mangone 2015, Tavtigian 2009). The variant was also identified in the following databases: dbSNP (ID: rs3218695) as "With Benign, Likely benign allele", ClinVar (4x, benign), and Clinvitae (3x, benign). The variant was not identified in Cosmic, MutDB, LOVD 3.0, or the ATM-LOVD databases. The variant was identified in control databases in 646 of 276916 chromosomes (8 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Observations by population include African in 567 of 24008 chromosomes (freq: 0.02), Other in 9 of 6464 chromosomes (freq: 0.001), Latino in 51 of 34412 chromosomes (freq: 0.001), European in 18 of 126598 chromosomes (freq: 0.0001), and South Asian in 1 of 30764 chromosomes (freq: 0.00003). The variant was not observed in the Ashkenazi Jewish, East Asian, or Finnish populations. The p.Asp814 residue is conserved in mammals but not in more distantly related organisms. However computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; 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 also 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) RCV001573497 SCV001799460 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120123 SCV001905837 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120123 SCV001958836 benign not specified no assertion criteria provided clinical testing

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