ClinVar Miner

Submissions for variant NM_006623.4(PHGDH):c.290+2T>C

dbSNP: rs886041874
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000313790 SCV000330660 pathogenic not provided 2016-07-06 criteria provided, single submitter clinical testing The c.290+2T>C variant in the PHGDH gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 2. 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.290+2T>C variant was not observed 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.290+2T>C as a pathogenic variant.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000415201 SCV000492522 likely pathogenic Seizure; Epileptic encephalopathy 2014-06-11 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001197384 SCV001368104 likely pathogenic PHGDH deficiency 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001197384 SCV002235628 pathogenic PHGDH deficiency 2022-04-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 280721). Disruption of this splice site has been observed in individual(s) with phosphoglycerate dehydrogenase deficiency or syndromic epilepsy (PMID: 29286531, 29703746). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change affects a donor splice site in intron 2 of the PHGDH 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 PHGDH are known to be pathogenic (PMID: 14645240, 24836451).
Genome-Nilou Lab RCV003338496 SCV004049049 likely pathogenic Neu-Laxova syndrome 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001197384 SCV004049050 likely pathogenic PHGDH deficiency 2023-04-11 criteria provided, single submitter clinical testing
Institute of Immunology and Genetics Kaiserslautern RCV001197384 SCV005043021 pathogenic PHGDH deficiency 2024-04-25 criteria provided, single submitter clinical testing ACMG Criteria: PM2, PVS1, PP5; Variant was found in heterozygous state

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