ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.2130+5G>A

dbSNP: rs777102890
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002533436 SCV000824766 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2021-01-19 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TERT-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change falls in intron 5 of the TERT gene. It does not directly change the encoded amino acid sequence of the TERT protein, but it affects a nucleotide within the consensus splice site of the intron.
Molecular Genetics, Royal Melbourne Hospital RCV002225114 SCV002503650 uncertain significance Dyskeratosis congenita 2023-03-30 criteria provided, single submitter clinical testing This sequence change falls in the splice region of the donor site of intron 5 of TERT. The variant is absent in a large population cohort (gnomAD v2.1 and v3.1), and has been classified as a variant of uncertain significance (ClinVar). The nucleotide is moderately conserved (100 vertebrates, UCSC), and multiple lines of computational evidence predict an impact on splicing (SpliceAI, MaxEntScan, NNSplice). Based on the classification scheme RMH Modified ACMG Guidelines v1.3.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, PP3.

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