ClinVar Miner

Submissions for variant NM_000170.3(GLDC):c.2203-2A>G

dbSNP: rs386833545
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049473 SCV000795388 pathogenic Glycine encephalopathy 2017-11-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000049473 SCV001587483 pathogenic Glycine encephalopathy 2023-12-13 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 18 of the GLDC 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 GLDC are known to be pathogenic (PMID: 16601880). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with non-ketotic hyperglycinemia (PMID: 26179960). 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: 56064). 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.
Revvity Omics, Revvity RCV000049473 SCV002024837 pathogenic Glycine encephalopathy 2019-09-23 criteria provided, single submitter clinical testing
GeneDx RCV004794356 SCV005414667 pathogenic not provided 2024-05-22 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16450403, 24407464, 12126939, 26179960)
Fulgent Genetics, Fulgent Genetics RCV005042157 SCV005679307 likely pathogenic Glycine encephalopathy 1 2024-01-26 criteria provided, single submitter clinical testing
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049473 SCV000081907 probable-pathogenic Glycine encephalopathy no assertion criteria provided not provided Converted during submission to Likely pathogenic.
Natera, Inc. RCV000049473 SCV002075741 pathogenic Glycine encephalopathy 2020-06-24 no assertion criteria provided clinical testing

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