Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000486129 | SCV000572227 | pathogenic | not provided | 2019-08-15 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678376 | SCV000804443 | likely pathogenic | Microcephaly 5, primary, autosomal recessive | 2017-06-28 | criteria provided, single submitter | provider interpretation | This 8 year old female with microcephaly (<2nd percentile) and intellectual disbality was found to carry a maternally inherited variant in the ASPM gene. The p.Leu2306SerfsX20 is absent from population databases. The variant is predicted to cause loss of normal protein function. She also carries a paternally inherited ASPM variant (p.Arg1818Cys), classified as a variant of uncertain significance. While homozygous or compound heterozygous variants in this gene are associated with autosomal recessive primary microcephaly, this patient also carries a maternally-inherited pathogenic variant in KIF11, which is currently thought to be the underlying genetic etiology for her microcephaly and intellectual disability. Individuals with this form of primary microcephaly have been noted to have narrow sloping foreheads; this patient and her mother are both noted to have sloping foreheads with bitemporal narrowing. |
| Genome- |
RCV000678376 | SCV004178596 | likely pathogenic | Microcephaly 5, primary, autosomal recessive | 2023-04-11 | criteria provided, single submitter | clinical testing |