Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Kids Neuroscience Centre, |
RCV001726495 | SCV001571490 | likely pathogenic | X-linked intellectual disability-cerebellar hypoplasia syndrome | criteria provided, single submitter | clinical testing | mRNA studies confirm the hemizygous OPHN1 c.702+4A>G variant induces abnormal splicing of OPHN1 transcripts in blood mRNA. OPHN1 exon-8 is a canonical exon included in all predominant OPHN1 isoforms expressed in brain. The absence of this variant from gnomAD is consistent with a rare X-linked recessive disorder. Exon 8 skipping induced by the OPHN1 c.702+4A>G variant abnormally removes 35 amino acids from the encoded Oligophrenin-1 protein. Hemizygous variants in OPHN1 are consistent with X-linked recessive mental retardation. |