Submissions for variant NM_001377.3(DYNC2H1):c.3302+1G>T

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003587687	SCV004313340	likely pathogenic	Jeune thoracic dystrophy	2023-12-12	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 22 of the DYNC2H1 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 DYNC2H1 are known to be pathogenic (PMID: 23339108, 32753734, 33755199). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV005001400	SCV005626382	likely pathogenic	Asphyxiating thoracic dystrophy 3	2025-01-15	criteria provided, single submitter	clinical testing