ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.1996C>T (p.Arg666Cys) (rs61760163)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000170374 SCV000222789 uncertain significance not specified 2014-01-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724215 SCV000224776 uncertain significance not provided 2018-04-17 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000170374 SCV000247316 uncertain significance not specified 2014-06-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000384253 SCV000362904 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000289884 SCV000362905 likely benign COFS syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000344840 SCV000362906 likely benign Cockayne syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000724215 SCV000572239 uncertain significance not provided 2020-12-28 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colorectal or other cancer (Castellanos 2017, Feliubadalo 2017, Nordfors 2018); This variant is associated with the following publications: (PMID: 29784668, 28051113, 29602769, 28050010, 30653986)
Fulgent Genetics,Fulgent Genetics RCV000515272 SCV000611388 uncertain significance DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome B; Lung carcinoma; UV-sensitive syndrome 1; Age-related macular degeneration 5; Premature ovarian failure 11 2017-05-23 criteria provided, single submitter clinical testing
Invitae RCV000724215 SCV001012455 likely benign not provided 2020-12-08 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000724215 SCV001714949 uncertain significance not provided 2020-06-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000724215 SCV001548968 uncertain significance not provided no assertion criteria provided clinical testing The ERCC6 p.Arg666Cys variant was identified in the literature in 1 of 28 proband chromosomes (frequency: 0.036) from individuals with a positive history of cancer (proband had colon cancer) (Castellanos_2017_PMID:28051113). The variant was identified in dbSNP (ID: rs61760163), LOVD 3.0 and ClinVar (classified as likely benign by Invitae and Illumina, and as uncertain significance by Claritas Genomics, Genetic Services Laboratory University of Chicago, Fulgent Genetics, EGL Genetic Diagnostics and GeneDx). The variant was identified in control databases in 498 of 282720 chromosomes (1 homozygous) at a frequency of 0.001761 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: Latino in 103 of 35438 chromosomes (freq: 0.002906), Other in 20 of 7220 chromosomes (freq: 0.00277), European (non-Finnish) in 318 of 129064 chromosomes (freq: 0.002464), Ashkenazi Jewish in 22 of 10368 chromosomes (freq: 0.002122), African in 16 of 24964 chromosomes (freq: 0.000641), European (Finnish) in 16 of 25116 chromosomes (freq: 0.000637) and South Asian in 3 of 30614 chromosomes (freq: 0.000098), but was not observed in the East Asian population. The p.Arg666 residue is conserved in mammals but not in more distantly related organisms, and four out of five 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 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000724215 SCV001798593 uncertain significance not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.