Submissions for variant NM_173076.3(ABCA12):c.5381+1G>C

dbSNP: rs1553523037

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000578636	SCV000680490	pathogenic	not provided	2020-08-21	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000578636	SCV004389991	likely pathogenic	not provided	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 34 of the ABCA12 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 ABCA12 are known to be pathogenic (PMID: 20672373). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ABCA12-related conditions. ClinVar contains an entry for this variant (Variation ID: 488673). 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.