Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002470454 | SCV002767926 | uncertain significance | Bosch-Boonstra-Schaaf optic atrophy syndrome | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_005654.5(NR2F1):c.344G>T in exon 1 of 3 of the NR2F1 gene. This substitution is predicted to create a major amino acid change from arginine to leucine at position 115 of the protein, NP_005645.1(NR2F1):p.(Arg115Leu). The arginine at this position has moderate conservation (100 vertebrates, UCSC), and is located within the DNA-binding functional domain. In silico software predicts this variant to be pathogenic (PolyPhen, SIFT, CADD, MutationTaster). The variant is not present in the gnomAD population database. It has not been previously reported in clinical cases. A different variant in the same codon resulting in a change to proline has been reported in patients with Bosch-Boonstra-Schaaf optic atrophy syndrome (ClinVar, Bosch, D. et al. (2014)). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with POTENTIAL CLINICAL RELEVANCE. |