Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000034052 | SCV000194323 | pathogenic | Orofaciodigital syndrome I | 2013-09-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000522417 | SCV000617387 | pathogenic | not provided | 2017-08-14 | criteria provided, single submitter | clinical testing | The c.877_878delAT variant in the OFD1 gene has been reported previously in two unrelated individuals with oral-facial-digital syndrome, type 1 (Prattichizzo et al., 2008). The c.877_878delAT variant causes a frameshift starting with codon Methionine 293, changes this amino acid to a Glycine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Met293GlyfsX15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.877_878delAT variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.877_878delAT as a pathogenic variant. |
Invitae | RCV001852687 | SCV002244045 | pathogenic | Familial aplasia of the vermis; Orofaciodigital syndrome I | 2021-06-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with oral-facial-digital syndrome type 1 (PMID: 18546297). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 41153). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met293Glyfs*15) in the OFD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OFD1 are known to be pathogenic (PMID: 16783569, 18546297, 27081566). |