Submissions for variant NM_005654.6(NR2F1):c.79G>C (p.Ala27Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002633756	SCV003515845	uncertain significance	not provided	2023-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 27 of the NR2F1 protein (p.Ala27Pro). 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 2196549). This variant has not been reported in the literature in individuals affected with NR2F1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database.
Neuberg Centre For Genomic Medicine, NCGM	RCV005208196	SCV005849274	uncertain significance	Bosch-Boonstra-Schaaf optic atrophy syndrome	2023-06-22	criteria provided, single submitter	clinical testing	The observed missense variant c.79G>C(p.Ala27Pro) in the NR2F1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is absnet in the gnomAD Exomes however this variant is covered in fewer than 50% of individuals in gnomAD v2.1.1 exomes. Allele frequency estimates may not be reliable. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Ala at position 27 is changed to a Pro changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Probably damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.