Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| New York Genome Center | RCV004555181 | SCV005044110 | pathogenic | Alveolar capillary dysplasia with pulmonary venous misalignment | 2022-03-04 | criteria provided, single submitter | clinical testing | The de novo c.802_805del (p.Ala268ProfsTer110) variant identified in the FOXF1 gene is the deletion of 4 nucleotides within exon 1 of 2 (amino acids 268-269/380), and is predicted to lead to a shift of the reading frame resulting in anomalous protein sequence and premature termination of the protein approximately 110 amino acids downstream. This variant is absent from population databases (gnomADv2, gnomADv3, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. While this variant is absent from ClinVar, many nonsense and frameshift variants downstream of the one identified here have been reported as Pathogenic or Likely Pathogenic (VarIDs:869492, 423429, 1302014, others). The p.Ala268ProfsTer110 variant identified here has not been reported previously in the literature, however a different de novo frameshift variant at the same amino acid, leading to a similar predicted consequence (c.802delG, (p.Ala268ArgfsTer111)) has been reported in an individual with histopathologically verified ACDMPV [Supp. Table E4; PMID:31199666]. Additional frameshift and nonsense variants C-terminal to the one identified here have also been reported in individuals with clinical and histopathologically confirmed ACDMPV [PMID:31199666, 19500772, 23505205, others]. Given its deleterious nature, presence de novo here, and absence in population databases, the de novo c.802_805del (p.Ala268ProfsTer110) variant identified in the FOXF1 gene is reported as Pathogenic. |