ClinVar Miner

Submissions for variant NM_022552.5(DNMT3A):c.1667+1G>A

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003584060 SCV004284458 likely pathogenic Tatton-Brown-Rahman overgrowth syndrome 2024-01-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 14 of the DNMT3A 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 DNMT3A are known to be pathogenic (PMID: 24614070). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with DNMT3A-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.

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