Submissions for variant NM_000123.4(ERCC5):c.2818G>A (p.Val940Met)

gnomAD frequency: 0.00113  dbSNP: rs146344855

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000625481	SCV000382119	likely benign	Xeroderma pigmentosum, group G	2017-05-01	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625481	SCV000745533	uncertain significance	Xeroderma pigmentosum, group G	2015-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763871	SCV000894806	uncertain significance	Xeroderma pigmentosum, group G; Cerebrooculofacioskeletal syndrome 3	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000897333	SCV001041474	likely benign	not provided	2023-12-30	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000897333	SCV002010218	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000897333	SCV002499841	likely benign	not provided	2022-04-15	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Sema4, Sema4	RCV002258872	SCV002532683	likely benign	Hereditary cancer-predisposing syndrome	2021-05-10	criteria provided, single submitter	curation
Ambry Genetics	RCV002520850	SCV003733751	likely benign	Inborn genetic diseases	2021-08-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000897333	SCV004010253	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ERCC5: BP4, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323507	SCV004030011	uncertain significance	not specified	2023-07-21	criteria provided, single submitter	clinical testing	Variant summary: ERCC5 c.2818G>A (p.Val940Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 251474 control chromosomes, including 1 homozygote, predominantly at a frequency of 0.0012 within the Non-Finnish European subpopulation in the gnomAD database. To our knowledge, no occurrence of c.2818G>A in individuals affected with Cerebrooculofacioskeletal Syndrome 3 and no experimental evidence demonstrating its impact on protein function have been reported. Ten submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as likely benign (n=6) or uncertain significance (n=4). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625481	SCV000745994	uncertain significance	Xeroderma pigmentosum, group G	2015-11-08	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003910155	SCV004722928	likely benign	BIVM-ERCC5-related disorder	2020-04-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).