Submissions for variant NM_005236.3(ERCC4):c.2545C>G (p.Gln849Glu)

gnomAD frequency: 0.00008  dbSNP: rs374186605

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000535348	SCV000654062	benign	Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q	2024-01-13	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257428	SCV002537949	uncertain significance	Xeroderma pigmentosum	2021-09-24	criteria provided, single submitter	curation
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470769	SCV002769370	likely benign	Fanconi anemia complementation group Q	2020-10-19	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as likely benign. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to glutamic acid (exon 11). (N) 0252 - Variant is homozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (23 heterozygotes, 1 homozygote). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (p.(Gln849Leu); 9 heterozygotes, 0 homozygotes). (N) 0503 - Missense variant consistently predicted to be tolerated or not conserved in mammals with a minor amino acid change. (B) 0600 - Variant is located in an annotated domain or motif (Rad1 superfamily; NCBI)(N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0806 - Moderate previous evidence of neutrality in unrelated individuals (ClinVar). (B) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is bialleic. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Ambry Genetics	RCV002515858	SCV003724213	uncertain significance	Inborn genetic diseases	2022-02-03	criteria provided, single submitter	clinical testing	The c.2545C>G (p.Q849E) alteration is located in exon 11 (coding exon 11) of the ERCC4 gene. This alteration results from a C to G substitution at nucleotide position 2545, causing the glutamine (Q) at amino acid position 849 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153389	SCV003843289	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315749	SCV004017498	likely benign	Xeroderma pigmentosum, group F	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000120810	SCV000084975	not provided	not specified	2013-09-19	no assertion provided	reference population