TERT NM_198253.2:c.3184G>A, Ala1062Thr

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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Variant classified as Uncertain Risk Allele. TERT c.3184G>A (p.Ala1062Thr) has been associated with increased risk for acute myeloid leukemia. This variant has been observed in multiple ethnic backgrounds with highest frequencies in individuals of non-Finnish European ancestry (2.1%, Genome Aggregation Database (gnomAD); rs35719940) and is present in ClinVar (ID: 39121). Several small studies implicate this variant is associated with 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). Functional studies from all but one group (Calado 2011) suggest that that this variant does not have a significant impact on telomerase activity (Alder 2008, Gramatges 2013, Zaug 2013, Zhang 2014, Hoffman 2017). In summary, it is uncertain if this variant is a risk factor for TERT-related conditions.