ClinVar Miner

Submissions for variant NM_203486.3(DLL3):c.395del (p.Gly132fs)

dbSNP: rs761454301
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV004527802 SCV000915832 uncertain significance DLL3-related disorder 2018-12-05 criteria provided, single submitter clinical testing The DLL3 c.395delG (p.Gly132GlufsTer109) variant results in a frameshift and is predicted to result in an absent or truncated protein, including loss of the delta-serrate-lag2 domain, all six EGF-like repeats, and the transmembrane and intracellular domains. This variant has been reported in a compound heterozygous state with a second frameshift variant in one individual with spondylocostal dysostosis (Turnpenny et al. 2003). The p.Gly132GlufsTer109 variant is reported at a frequency of 0.001015 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the available evidence and the potential impact of frameshift variants, the p.Gly132GlufsTer109 variant is classified as a variant of unknown significance but suspicious for pathogenicity for DLL3-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV002535650 SCV003443254 pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly132Glufs*109) in the DLL3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DLL3 are known to be pathogenic (PMID: 12746394). This variant is present in population databases (rs761454301, gnomAD 0.1%). This premature translational stop signal has been observed in individual(s) with spondylocostal dysostosis (PMID: 12746394). ClinVar contains an entry for this variant (Variation ID: 632311). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV003485641 SCV004234314 pathogenic Spondylocostal dysostosis 1, autosomal recessive 2023-03-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV003485641 SCV005648750 pathogenic Spondylocostal dysostosis 1, autosomal recessive 2024-06-22 criteria provided, single submitter clinical testing

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