Submissions for variant NM_000123.4(ERCC5):c.56C>T (p.Pro19Leu)

gnomAD frequency: 0.00059  dbSNP: rs34291397

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000995079	SCV001149074	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	ERCC5: BP4
Illumina Laboratory Services, Illumina	RCV001109705	SCV001267068	uncertain significance	Xeroderma pigmentosum, group G	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Baylor Genetics	RCV001293875	SCV001482537	uncertain significance	Cerebrooculofacioskeletal syndrome 3	2020-08-30	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000995079	SCV002010212	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Invitae	RCV000995079	SCV002126452	uncertain significance	not provided	2022-08-23	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 19 of the ERCC5 protein (p.Pro19Leu). This variant is present in population databases (rs34291397, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ERCC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 134159). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics	RCV002517588	SCV003629056	uncertain significance	Inborn genetic diseases	2021-11-25	criteria provided, single submitter	clinical testing	The c.56C>T (p.P19L) alteration is located in exon 1 (coding exon 1) of the ERCC5 gene. This alteration results from a C to T substitution at nucleotide position 56, causing the proline (P) at amino acid position 19 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000995079	SCV003921541	uncertain significance	not provided	2023-04-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30086788, 29641532, 27498913, 28137924, 24728327, 31937788, 30306255, 33821390)
ITMI	RCV000120832	SCV000084997	not provided	not specified	2013-09-19	no assertion provided	reference population