Submissions for variant NM_004364.5(CEBPA):c.568T>C (p.Ser190Pro)

gnomAD frequency: 0.00003  dbSNP: rs867463920

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001306460	SCV001495834	uncertain significance	Acute myeloid leukemia	2021-04-23	criteria provided, single submitter	clinical testing	This sequence change replaces serine with proline at codon 190 of the CEBPA protein (p.Ser190Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CEBPA-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003238343	SCV002009841	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing