Submissions for variant NM_198253.3(TERT):c.219+7C>T

gnomAD frequency: 0.00034  dbSNP: rs573817924

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000266345	SCV000452715	likely benign	Aplastic anemia	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000324023	SCV000452716	likely benign	Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000357781	SCV000452717	likely benign	Dyskeratosis congenita, autosomal dominant 2	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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002520305	SCV000561721	likely benign	Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis	2024-01-29	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000613962	SCV000713725	likely benign	not specified	2017-10-26	criteria provided, single submitter	clinical testing	c.219+7C>T in Intron 1 of TERT: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.07% (46/70754) o f European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad .broadinstitute.org; dbSNP rs573817924). ACMG/AMP Criteria applied: BP4, BP7 (Ri chards 2015).
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000613962	SCV002550453	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004559045	SCV002724905	uncertain significance	Dyskeratosis congenita	2014-10-15	criteria provided, single submitter	clinical testing	The c.219+7C>T intronic variant results from a C to T substitution 7 nucleotides after coding exon 1 in the TERT gene. This variant was first identified in a 13 year old female who was diagnosed with Diamond Blackfan anemia at 6 months of age and was transfusion dependent and had telomere lengths below the first percentile; this variant was also identified in her reportedly healthy father, who had telomere lengths near the first percentile. In addition, both carried a promoter variant, c.-171A>T, in the DKC1 gene; however, authors felt neither variant explained the clinical picture of the affected daughter (Pavesi E et al. Pediatr Blood Cancer. 2009;53(3):411-6). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 3491 samples (6982 alleles) with coverage at this position. This nucleotide position is not well conserved in available vertebrate species on limited alignment. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this donor splice site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528455	SCV001740239	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528455	SCV001972229	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544655	SCV004788738	likely benign	TERT-related disorder	2020-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).