Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics Munich, |
RCV000995706 | SCV001150026 | pathogenic | Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities | 2019-09-17 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001089771 | SCV001238758 | pathogenic | not provided | 2020-04-07 | criteria provided, single submitter | clinical testing | The N807K variant in the BCL11B gene has been reported previously as a de novo variant in a child with developmental delay, dysmorphic facial features, dental anomalies, feeding anomalies, and low T-cell receptor excision circle (TREC) analysis at birth (Lessel et al., 2018). The variant is not observed in large population cohorts (Lek et al., 2016). The N807K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret N807K as a pathogenic variant. |
| Broad Center for Mendelian Genomics, |
RCV000995706 | SCV001430759 | likely pathogenic | Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities | 2020-05-29 | criteria provided, single submitter | research | The heterozygous p.Glu879Asp variant in BCL11B was identified by our study in 1 individual with intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities (PMID: 29985992). Trio genome analysis showed this variant to be de novo in 1 individual. This variant was absent from large population studies. The p.Asn807Lys variant is located in a region of BCL11B that is essential to protein folding and stability, suggesting that this variant is in a functional domain and slightly supports pathogenicity (PMID: 29985992). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PS2, PM2, PM1_supporting (Richards 2015). |
| Baylor Genetics | RCV000995706 | SCV001748914 | likely pathogenic | Intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities | 2021-06-10 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000678214 | SCV000804216 | pathogenic | Immunodeficiency 49 | 2018-08-28 | no assertion criteria provided | literature only |