ClinVar Miner

Submissions for variant NM_000392.5(ABCC2):c.3258+1G>A

gnomAD frequency: 0.00017  dbSNP: rs762243203
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000593091 SCV000703434 pathogenic not provided 2018-04-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000593091 SCV001577103 pathogenic not provided 2024-09-23 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 23 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 (rs762243203, gnomAD 0.02%). Disruption of this splice site has been observed in individuals with clinical features of Dubin-Johnson syndrome (PMID: 23429660, 34858902; internal data). ClinVar contains an entry for this variant (Variation ID: 498429). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000593091 SCV002558263 pathogenic not provided 2022-01-31 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; This variant is associated with the following publications: (PMID: 34858902, 23429660, 34426522, 31589614, 26689913)
Mayo Clinic Laboratories, Mayo Clinic RCV000593091 SCV004226615 likely pathogenic not provided 2022-07-01 criteria provided, single submitter clinical testing PM2, PM3_supporting, PVS1
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV004760639 SCV005374312 pathogenic Dubin-Johnson syndrome 2024-09-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV004760639 SCV005664883 likely pathogenic Dubin-Johnson syndrome 2024-05-07 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004745495 SCV005350904 pathogenic ABCC2-related disorder 2024-06-04 no assertion criteria provided clinical testing The ABCC2 c.3258+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant, in the homozygous condition or along with a second variant in this gene, has been reported in 2 patients with Dubin-Johnson syndrome (Sticova et al. 2013. PubMed ID: 23429660; Al-Hussaini et al. 2021. PubMed ID: 34858902). This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD. Variants that disrupt the consensus splice donor site in ABCC2 are expected to be pathogenic. This variant is interpreted as pathogenic.

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