ClinVar Miner

Submissions for variant NM_000170.2(GLDC):c.2665+1G>C (rs149070244)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000353440 SCV000329725 pathogenic not provided 2016-01-12 criteria provided, single submitter clinical testing The c.2665+1G>C pathogenic variant in the GLDC gene has been reported previously in the heterozygous state in a patient with nonketotic hyperglycinemia, in whom a second pathogenic variant was not detected (Kure et al., 2006). This splice site variant destroys the canonical splice donor site in intron 22. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.2665+1G>C variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2665+1G>C as a pathogenic variant.
Counsyl RCV000411816 SCV000486117 likely pathogenic Non-ketotic hyperglycinemia 2016-11-11 criteria provided, single submitter clinical testing
Invitae RCV000411816 SCV000636393 pathogenic Non-ketotic hyperglycinemia 2019-09-10 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 22 of the GLDC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880, 16450403). This particular variant has been reported in the literature in individuals affected with nonketotic hyperglycinemia (PMID: 16450403). This variant was also found in individuals with suspected nonketotic hyperglycinemia where it has been observed on the opposite chromosome (in trans) from other pathogenic variants (PMID: 27362913). For these reasons, this variant has been classified as Pathogenic.

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