ClinVar Miner

Submissions for variant NM_000123.4(ERCC5):c.3177C>T (p.Gly1059=) (rs148856875)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000625482 SCV000745535 likely benign Xeroderma pigmentosum, group G 2015-09-21 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000625482 SCV000745995 likely benign Xeroderma pigmentosum, group G 2015-07-21 criteria provided, single submitter clinical testing
Invitae RCV000861317 SCV001001592 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000625482 SCV001270316 likely benign 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000861317 SCV001553999 likely benign not provided no assertion criteria provided clinical testing The ERCC5 p.Gly1059Gly variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs148856875), LOVD 3.0 and in ClinVar (classified as likely benign by Erasmus Medical Center DNA and Cytogenetics Diagnostics Unit and VU University Medical Center Amsterdam Genome Diagnotics Laboratory). The variant was identified in control databases in 681 of 282376 chromosomes (3 homozygous) at a frequency of 0.002412 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Ashkenazi Jewish in 267 of 10350 chromosomes (freq: 0.0258), Other in 29 of 7208 chromosomes (freq: 0.004023), European (non-Finnish) in 289 of 128834 chromosomes (freq: 0.002243), South Asian in 44 of 30604 chromosomes (freq: 0.001438), European (Finnish) in 26 of 25116 chromosomes (freq: 0.001035), Latino in 21 of 35408 chromosomes (freq: 0.000593) and African in 5 of 24914 chromosomes (freq: 0.000201); it was not observed in the East Asian population. The p.Gly1059Gly variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (MaxEntScan, NNSPLICE) predict a greater than 10% difference in splicing and the creation of a new 5' splice site; 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.

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