Submissions for variant NM_001099274.3(TINF2):c.507+6G>A

gnomAD frequency: 0.00020  dbSNP: rs142144996

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001050306	SCV001214405	uncertain significance	Dyskeratosis congenita	2024-10-08	criteria provided, single submitter	clinical testing	This sequence change falls in intron 4 of the TINF2 gene. It does not directly change the encoded amino acid sequence of the TINF2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs142144996, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with TINF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 846889). Variants that disrupt 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 is not likely to affect RNA splicing. 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.
Genetic Services Laboratory, University of Chicago	RCV001819767	SCV002066739	uncertain significance	not specified	2020-12-18	criteria provided, single submitter	clinical testing	This change does not appear to have been previously described in patients with TINF2-related disorders and has been described in the gnomAD with a low population frequency of 0.050% in the African sub population (dbSNP rs142144996). This sequence change is not clearly predicted to have a deleterious effect on splicing based on in silico splice prediction programs. It is possible that this sequence change represents a benign sequence change in the TINF2 gene that has not been identified to date. The functional significance of this sequence change is not known at present and its contribution to this patient's disease phenotype cannot definitively be determined.
PreventionGenetics, part of Exact Sciences	RCV003963010	SCV004779303	likely benign	TINF2-related disorder	2022-01-21	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).