ClinVar Miner

Submissions for variant NM_024884.3(L2HGDH):c.256+1G>A (rs150299874)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438376 SCV000517201 pathogenic not provided 2015-05-12 criteria provided, single submitter clinical testing The c.256+1G>A variant in the L2HGDH gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. This splice site variant destroys the canonicalsplice donor site in intron 2. It is predicted to cause abnormal gene splicing, either leading to an abnormalmessage that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if themessage is used for protein translation. The c.256+1G>A substitution was not observed at any significantfrequent in approximately 6,500 individuals of European and African American ancestry in the NHLBIExome Sequencing Project, indicating it is not a common benign variant in these populations. We interpretc.256+1G>A as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000763339 SCV000894021 pathogenic L-2-hydroxyglutaric aciduria 2018-10-31 criteria provided, single submitter clinical testing
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000763339 SCV001134999 pathogenic L-2-hydroxyglutaric aciduria 2019-11-05 criteria provided, single submitter clinical testing A homozygous 5' splice site variation in intron 2 of the L2HGDH gene that affects the invariant GT donor splice site of exon 2 was detected. The observed variant has not been reported in the 1000 genomes and has a minor allele frequency of 0.002% in the ExAC databases. The in silico prediction of the variant is damaging by MutationTaster2. The reference codon is conserved across species. In summary, c.256+1G>A variant meets our criteria to be classified as a pathogenic.

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