Submissions for variant NM_000392.5(ABCC2):c.1531-2A>G

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003729105	SCV004533014	likely pathogenic	not provided	2023-12-23	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 11 of the ABCC2 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 ABCC2 are known to be pathogenic (PMID: 9185779, 16549534, 16952291). This variant is present in population databases (rs753329079, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with ABCC2-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.
PreventionGenetics, part of Exact Sciences	RCV003966639	SCV004779293	likely benign	ABCC2-related disorder	2022-09-01	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).