Submissions for variant NM_021922.3(FANCE):c.164G>A (p.Trp55Ter)

dbSNP: rs2150885915

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV001818009	SCV002065820	likely pathogenic	not provided	2021-04-26	criteria provided, single submitter	clinical testing	DNA sequence analysis of the FANCE gene demonstrated a sequence change, c.164G>A, which results in the creation of a premature stop codon at amino acid position 55, p.Trp55*. This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated FANCE protein with potentially abnormal function. This sequence change does not appear to have been previously described in patients with FANCE-related disorders, but other downstream truncating variants have been described in patients with Fanconi anemia (PMID: 11001585). This sequence change was absent in the gnomAD population database. Collectively these evidences suggest that, the p.Trp55* change is likely pathogenic, however functional studies have not been performed to prove this conclusively.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003509701	SCV004353341	pathogenic	Fanconi anemia complementation group E	2023-04-06	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1338638). This variant has not been reported in the literature in individuals affected with FANCE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp55*) in the FANCE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCE are known to be pathogenic (PMID: 11001585, 17924555).