Submissions for variant NM_005236.3(ERCC4):c.1787C>A (p.Ala596Glu)

gnomAD frequency: 0.00001  dbSNP: rs751782722

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000820566	SCV000961283	uncertain significance	Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q	2022-12-13	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ERCC4 protein function. ClinVar contains an entry for this variant (Variation ID: 662825). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. This variant is present in population databases (rs751782722, gnomAD 0.04%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 596 of the ERCC4 protein (p.Ala596Glu).
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153866	SCV003843652	likely pathogenic	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing