Submissions for variant NM_006019.4(TCIRG1):c.2119-2A>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003557627	SCV004294905	likely pathogenic	not provided	2023-03-18	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant is also known as c.2116-2A>C. Disruption of this splice site has been observed in individual(s) with TCIRG1-related conditions (PMID: 22231430). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 17 of the TCIRG1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TCIRG1 are known to be pathogenic (PMID: 10888887, 10942435, 11532986, 19448635).
Baylor Genetics	RCV004574105	SCV005052952	likely pathogenic	Autosomal recessive osteopetrosis 1	2023-12-21	criteria provided, single submitter	clinical testing