ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.3122A>C (p.Gln1041Pro) (rs139007661)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000170382 SCV000222799 uncertain significance not specified 2014-01-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724216 SCV000226717 uncertain significance not provided 2018-04-17 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000170382 SCV000247318 uncertain significance not specified 2014-06-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000358951 SCV000362812 likely benign COFS syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000266566 SCV000362813 likely benign Cockayne syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000323987 SCV000362814 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000724216 SCV000572238 likely benign not provided 2020-12-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 29602769, 24036952, 28051113)
Fulgent Genetics,Fulgent Genetics RCV000515412 SCV000611389 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 RCV000724216 SCV001012454 benign not provided 2020-12-08 criteria provided, single submitter clinical testing
Mendelics RCV000988355 SCV001138043 uncertain significance DE SANCTIS-CACCHIONE SYNDROME 2019-05-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000724216 SCV001551323 uncertain significance not provided no assertion criteria provided clinical testing The ERCC6 p.Gln1041Pro 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: rs139007661), LOVD 3.0 and ClinVar (classified as benign by Invitae, likely benign by Illumina and uncertain significance by Claritas Genomics, Genetics Services Laboratory University of Chicago, Fulgent Genetics, EGL Genetic Diagnostics and GeneDx). The variant was identified in control databases in 492 of 282474 chromosomes (1 homozygous) at a frequency of 0.001742 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 102 of 35408 chromosomes (freq: 0.002881), Other in 20 of 7200 chromosomes (freq: 0.002778), European (non-Finnish) in 317 of 128972 chromosomes (freq: 0.002458), Ashkenazi Jewish in 22 of 10362 chromosomes (freq: 0.002123), European (Finnish) in 15 of 25090 chromosomes (freq: 0.000598), African in 13 of 24904 chromosomes (freq: 0.000522), South Asian in 3 of 30588 chromosomes (freq: 0.000098), but was not observed in the East Asian population. The p.Gln1041 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out 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.

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