Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004035368 | SCV003703372 | likely benign | Primary ciliary dyskinesia | 2022-06-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Labcorp Genetics |
RCV003770338 | SCV004572319 | uncertain significance | Familial aplasia of the vermis; Orofaciodigital syndrome I | 2024-11-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 890 of the OFD1 protein (p.Arg890Gln). This variant is present in population databases (rs748643730, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 978411). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt OFD1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004800761 | SCV005423376 | likely benign | not specified | 2024-10-04 | criteria provided, single submitter | clinical testing | Variant summary: OFD1 c.2669G>A (p.Arg890Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.9e-05 in 1203471 control chromosomes, predominantly at a frequency of 0.00033 within the African or African-American subpopulation in the gnomAD database (v4.1 dataset), including 6 hemizygotes. To our knowledge, no occurrence of c.2669G>A in individuals affected with Orofaciodigital Syndrome I and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 978411). Based on the evidence outlined above, the variant was classified as likely benign. |
| Service de Génétique Moléculaire, |
RCV001257024 | SCV001433580 | uncertain significance | Rare genetic intellectual disability | no assertion criteria provided | clinical testing |