Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics, |
RCV000991289 | SCV001055691 | likely benign | De Lange syndrome | 2019-12-12 | criteria provided, single submitter | clinical testing | The c.7697A>G NIPBL-variant (p.Lys2566Arg) is found at a relatively low frequency (gnomAD & ExAC population frequency <0.001 %) within the general population but has a pathogenic computational verdict due to 7 pathogenic predictions from DANN, EIGEN, FATHMM-MKL, M-CAP, MVP, MutationTaster and PrimateAI vs 3 benign predictions from DEOGEN2, MutationAssessor, and SIFT. The nucleotide and amino acid are highly conserved. In our facility, the variant was found in an affected patient with mental retardation, epilepsy, and obesity. Segregation analysis revealed the same variant in the unaffected, healthy brother. Thus, we consider this variant a rare benign polymorphism. |