ClinVar Miner

Submissions for variant NM_000400.3(ERCC2):c.594+2_594+5del (rs762309206)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000454337 SCV000538021 likely pathogenic Trichothiodystrophy 1, photosensitive 2015-12-04 criteria provided, single submitter clinical testing The c.594+2_594+5delTGAG splice-donor variant in the ERCC2 gene has not been previously reported. There has been a splice-donor variant in intron 7 of the ERCC2 gene observed in one affected individual with Trichothiodystrophy and was predicted to be a null allele. The affected individual was heterozygous for the splice-donor variant but also harbored a missense variant of unknown significance in the ERCC2 gene (Viprakasit et al., 2001). Although missense variants are a common mechanism for disease, loss of function variants have been reported in individuals affected with Xeroderma Pigmentosum. The c.594+2_594+5delTGAG splice-donor variant is present at a very low frequency in the three control population databases (Exome Sequencing Project [ESP], 1000 Genomes, and ExAc). Computational algorithms predict evolutionary conservation at this locus and a loss of the splice-donor site resulting in intron retention and introduction of a premature termination codon. In summary, this collective evidence supports the provisional classification of the c.594+2_594+5delTGAG variant as Likely Pathogenic
Knight Diagnostic Laboratories,Oregon Health and Sciences University RCV000454224 SCV000538022 likely pathogenic Xeroderma pigmentosum, group D 2015-12-04 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000599593 SCV000704022 likely pathogenic not provided 2016-11-30 criteria provided, single submitter clinical testing
GeneDx RCV000599593 SCV000709929 likely pathogenic not provided 2018-02-20 criteria provided, single submitter clinical testing The c.594+2_594+5delTGAG variant in the ERCC2 gene has been reported previously in an affected individual with trichothiodystrophy who was heterozygous for the c.594+2_594+5delTGAG variant and a missense variant (Viprakasit et al., 2001). This splice site variant destroys the canonical splice donor site in intron 7, which is predicted to cause abnormal gene splicing. The c.594+2_594+5delTGAG variant is observed in 20/276702 (0.007%) alleles in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). We interpret c.594+2_594+5delTGAG as a likely pathogenic variant.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000599593 SCV001151956 likely pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing

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