ClinVar Miner

Submissions for variant NM_003238.6(TGFB2):c.346+1G>A

dbSNP: rs1553292145
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519784 SCV000622027 likely pathogenic not provided 2019-11-11 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001853701 SCV002259952 likely pathogenic Loeys-Dietz syndrome 4 2021-04-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 1 of the TGFB2 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 TGFB2 are known to be pathogenic (PMID: 22772368, 22772371, 30739908). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with thoracic aortic aneurysm and/or dissection (PMID: 30739908). ClinVar contains an entry for this variant (Variation ID: 453158). 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. 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.

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