ClinVar Miner

Submissions for variant NM_198253.2(TERT):c.3184G>A (p.Ala1062Thr) (rs35719940)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000151992 SCV000605361 uncertain significance not specified 2016-11-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000151992 SCV000702134 benign not specified 2016-10-26 criteria provided, single submitter clinical testing
GeneReviews RCV000032393 SCV000056049 pathologic Aplastic anemia 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000032393 SCV000452227 likely benign Aplastic anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000395635 SCV000452228 likely benign Idiopathic fibrosing alveolitis, chronic form 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000305704 SCV000452229 likely benign Dyskeratosis Congenita, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000232252 SCV000291872 benign Idiopathic fibrosing alveolitis, chronic form; Dyskeratosis congenita, autosomal dominant, 2 2017-08-21 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151992 SCV000200551 not provided not specified 2015-09-02 no assertion provided clinical testing The p.Ala1062Thr variant in TERT is prevalent in the general population with frequencies up to ~2% (1300/61576) in European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35719940). Although this variant is not expected to cause highly penetrant, Mendelian disease, several studies indicate this variant as a risk allele for a number of different hematological and pulmonary conditions including pulmonary fibrosis (Tsakiri 2007, Alder 2008), AML (Calado 2009, Aref 2014), DL-BCL and CLL (Hills 2009) and cirrhosis (Calado 2011). These diseases are known to have an increased prevalence among a Mendelian, TERT related premature ageing syndrome (dyskeratosis congenita). Functional assays have shown conflicting results regarding the impact of this variant on telomerase activity (Alder 2008, Calado 2009, Calado 2009, Gramatges 2013, Zaug 2013, Zhang 2014). In summary, this variant may be a risk factor for TERT-related disease. It is not expected to lead to disease on its own but may act in conjunction with other genetic and/or environmental risk factors.
OMIM RCV000030632 SCV000053310 risk factor Leukemia, acute myeloid, susceptibility to 2009-01-27 no assertion criteria provided literature only
PreventionGenetics RCV000151992 SCV000316921 likely benign not specified criteria provided, single submitter clinical testing

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