ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1986T>C (p.Phe662=) (rs1800055)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122829 SCV000166086 benign Ataxia-telangiectasia syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000211971 SCV000167067 benign not specified 2014-01-17 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 RCV000123724 SCV000213136 likely benign Hereditary cancer-predisposing syndrome 2014-08-07 criteria provided, single submitter clinical testing
Color RCV000123724 SCV000537413 likely benign Hereditary cancer-predisposing syndrome 2015-08-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000586136 SCV000602570 likely benign not provided 2017-05-09 criteria provided, single submitter clinical testing The c.1986T>C variant (rs1800055) does not alter the amino acid sequence of the ATM protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with ataxia-telangiectasia or primary antibody deficiency in medical literature or in gene specific variation databases. This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.04 percent (identified on 5 out of 12,998 chromosomes) and is listed in the Exome Aggregation Consortium Browser with an overall population frequency of 0.042 percent (identified on 51 out of 121,356 chromosomes). Based on these observations, the c.1986T>C variant is likely to be benign.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000123724 SCV000679688 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000211971 SCV000694206 benign not specified 2019-02-14 criteria provided, single submitter clinical testing Variant summary: ATM c.1986T>C alters a conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00048 in 277242 control chromosomes, predominantly at a frequency of 0.0011 within the Ashkenazi Jewish subpopulation and at a frequency of 0.00083 in the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish and Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Breast Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism. c.1986T>C has been reported in the literature in individuals affected with cancer, including breast cancer, non-Hodgkin lymphoma and chronic lymphocytic leukemia (Skowronska_2012, Bernstein_2010, Sipahimalani_2007, Vorechovsky_1996). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. Co-occurrences with other pathogenic variants have been reported in our internal database (PALB2 c.761C>G, p.Ser254X; BRCA1 c.68_69delAG, p.E23fs*17), providing supporting evidence for a benign role. Additionally, the variant was detected in heterozygous state in 12 control individuals in the FLOSSIES database (individuals aged over 70 who never had cancer), providing further supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Counsyl RCV000122829 SCV000788483 likely benign Ataxia-telangiectasia syndrome 2018-03-29 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000586136 SCV001143098 benign not provided 2018-11-23 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000586136 SCV001148406 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000122829 SCV001266061 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
True Health Diagnostics RCV000123724 SCV000787848 likely benign Hereditary cancer-predisposing syndrome 2017-11-09 no assertion criteria provided clinical testing

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