ClinVar Miner

Submissions for variant NM_024079.5(ALG8):c.368+2T>G

gnomAD frequency: 0.00001  dbSNP: rs756894409
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070562 SCV001235816 likely pathogenic ALG8 congenital disorder of glycosylation 2019-12-04 criteria provided, single submitter clinical testing 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ALG8 are known to be pathogenic (PMID: 19862844). 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. This variant has not been reported in the literature in individuals with ALG8-related conditions. This variant is present in population databases (rs756894409, ExAC 0.001%). This sequence change affects a donor splice site in intron 3 of the ALG8 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Fulgent Genetics, Fulgent Genetics RCV002489709 SCV002802828 likely pathogenic ALG8 congenital disorder of glycosylation; Polycystic liver disease 3 with or without kidney cysts 2022-05-18 criteria provided, single submitter clinical testing
GeneDx RCV004773292 SCV005387100 likely pathogenic not provided 2024-02-12 criteria provided, single submitter clinical testing Identified as heterozygous in an adult female proband with polycystic liver and kidney disease, and additional individuals with unspecified kidney disorders, reported in the published literature (PMID: 36574950); 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 36574950)

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