Description
The TERT p.Glu441del variant was identified in the literature in two patients with aplastic anemia, a patient with acute myeloid leukemia and another patient with cirrhosis caused by alcohol (Yamaguchi_2005_PMID:15814878; Calado_2009_PMID:19674077; Calado_2009_PMID:19147845; Calado_2011_PMID:21520173). The variant was identified in dbSNP (ID: rs377639087), Cosmic, LOVD 3.0 and ClinVar (classified as likely benign by GeneDx, Invitae, Laboratory for Molecular Medicine, Illumina and Genetic Services Laboratory, University of Chicago and as uncertain significance by EGL Genetics and Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago). The variant was identified in control databases in 311 of 180940 chromosomes at a frequency of 0.001719 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 261 of 72072 chromosomes (freq: 0.003621), Other in 14 of 5334 chromosomes (freq: 0.002625), Ashkenazi Jewish in 9 of 8490 chromosomes (freq: 0.00106), European (Finnish) in 10 of 18616 chromosomes (freq: 0.000537), Latino in 11 of 25422 chromosomes (freq: 0.000433), African in 5 of 15812 chromosomes (freq: 0.000316) and South Asian in 1 of 22778 chromosomes (freq: 0.000044), but was not observed in the East Asian population. This variant is an in-frame deletion resulting in the removal of a glutamic acid (glu) residue at codon 441; the impact of this alteration on TERT protein function is not known. Functional studies have shown no association with telomere shortening but a decrease in telomere activity has been reported (Yamaguchi_2005_PMID:15814878; Calado_2009_PMID:19147845). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
