Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Human Genome Lab, |
RCV003232905 | SCV003928208 | likely pathogenic | Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 | criteria provided, single submitter | clinical testing | The stop gained NM_001759.4(CCND2):c.812C>A (p.Ser271Ter) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser271Ter variant is novel (not in any individuals) in 1kG All. The p.Ser271Ter variant is novel (not in any individuals) in gnomAD as well as in our inhouse database. This variant is predicted to cause loss of normal protein function through protein truncation. There are 2 downstream pathogenic loss of function variants, with the furthest variant being 6 residues downstream of this variant. This indicates that the region is critical to protein function. The gene CCND2 has a low rate of benign loss of function variants as indicated by a low upper bound of the observed/expected confidence interval 0.23. The p.Ser271Ter variant is a loss of function variant in the gene CCND2, which is intolerant of Loss of Function variants, as indicated by the presence of existing pathogenic loss of function variant NP_001750.1:p.Q265* and 2 others. In addition, the clinical phenotype of the proband matches with that of the disorder caused by pathogenic variants in CCND2 gene. For these reasons, this variant has been classified as Likely Pathogenic. |