ClinVar Miner

Submissions for variant NM_000122.2(ERCC3):c.2111C>T (p.Ser704Leu) (rs4150521)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000861013 SCV001001212 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000986805 SCV001135938 likely benign Xeroderma pigmentosum, complementation group b 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000861013 SCV001152396 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000986805 SCV001292700 likely benign Xeroderma pigmentosum, complementation group b 2017-04-27 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.
GeneDx RCV000861013 SCV001814079 likely benign not provided 2021-01-08 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: 28259476, 27153395, 31346352, 30256826, 16550608, 30414346, 16574953, 24728327)
ITMI RCV000120792 SCV000084956 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000861013 SCV001549770 likely benign not provided no assertion criteria provided clinical testing The ERCC3 p.Ser640Leu variant was not identified in the literature but was identified in dbSNP (ID: rs4150521) and ClinVar (classified as benign by Invitae; likely benign by Mendelics for Xeroderma pigmentosum, complementation group b and uncertain significance by CeGaT Praxis fuer Humangenetik Tuebingen). The variant was identified in control databases in 607 of 268178 chromosomes (2 homozygous) at a frequency of 0.002263 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (Finnish) in 182 of 25100 chromosomes (freq: 0.007251), Other in 32 of 6702 chromosomes (freq: 0.004775), Latino in 103 of 35102 chromosomes (freq: 0.002934), European (non-Finnish) in 257 of 118038 chromosomes (freq: 0.002177), Ashkenazi Jewish in 12 of 9854 chromosomes (freq: 0.001218), African in 12 of 23604 chromosomes (freq: 0.000508) and South Asian in 9 of 30526 chromosomes (freq: 0.000295), but was not observed in the East Asian population. The p.Ser640 residue is conserved in mammals but not in more distantly related organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000861013 SCV001809766 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000861013 SCV001967009 uncertain significance not provided no assertion criteria provided clinical testing

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