Submissions for variant NM_014844.5(TECPR2):c.2394+3A>G

gnomAD frequency: 0.00005  dbSNP: rs776681603

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848252	SCV002105929	uncertain significance	Hereditary spastic paraplegia	2019-10-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002545261	SCV003274790	uncertain significance	Hereditary spastic paraplegia 49	2022-02-23	criteria provided, single submitter	clinical testing	This sequence change falls in intron 9 of the TECPR2 gene. It does not directly change the encoded amino acid sequence of the TECPR2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs776681603, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with TECPR2-related conditions. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003401754	SCV004135228	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	TECPR2: BP4
PreventionGenetics, part of Exact Sciences	RCV003923336	SCV004745219	likely benign	TECPR2-related disorder	2019-05-24	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).