ClinVar Miner

Submissions for variant NM_001182.5(ALDH7A1):c.246+1G>A

gnomAD frequency: 0.00001  dbSNP: rs764588746
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519378 SCV000616927 likely pathogenic not provided 2024-08-21 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon 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: 31589614, 25525159, 20814824)
Labcorp Genetics (formerly Invitae), Labcorp RCV000791513 SCV000930765 pathogenic Pyridoxine-dependent epilepsy 2024-02-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the ALDH7A1 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 ALDH7A1 are known to be pathogenic (PMID: 16491085, 20554659). This variant is present in population databases (rs764588746, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with pyridoxine-dependent epilepsy (PMID: 20814824; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 449124). 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.
Genome-Nilou Lab RCV000791513 SCV004050298 likely pathogenic Pyridoxine-dependent epilepsy 2023-04-11 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000791513 SCV005672275 pathogenic Pyridoxine-dependent epilepsy 2024-01-02 criteria provided, single submitter clinical testing
Center of Excellence for Medical Genomics, Chulalongkorn University RCV000791513 SCV002570064 pathogenic Pyridoxine-dependent epilepsy 2002-09-08 no assertion criteria provided research

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